X-linked disease

This early-stage study tests a new drug called SR604 in healthy people and those with hemophilia A, B, or factor VII deficiency. The main goal is to check safety and how the drug moves through the body. About 31 participants will receive single or multiple doses to find the right…

This study tests whether programming a cochlear implant based on each person's unique inner ear structure improves hearing compared to the standard one-size-fits-all approach. Adults with severe to profound hearing loss who already have a MED-EL cochlear implant will receive both…

This study looks at whether Emicizumab, a newer drug, prevents bleeding during sports better than standard Factor VIII in children with moderate to severe hemophilia A. About 72 kids aged 6 to 19 who already play sports and take one of these drugs will be followed. The goal is to…

This study looks at the long-term safety and effectiveness of a medicine called marstacimab for people with severe hemophilia A or B. Participants receive regular injections to help prevent bleeding episodes. The goal is to see if this treatment is safe and reduces bleeds over ti…

This expanded access program provides bitopertin (DISC-1459) to patients aged 12 and older with erythropoietic protoporphyria (EPP) or X-linked protoporphyria (XLP) who have no satisfactory treatment options in the US. The goal is to offer access and gather safety information. Pa…

This study tests Mim8, a drug that helps blood clot by mimicking a missing protein, in people with hemophilia A (with or without inhibitors). Over 450 participants will receive injections for up to 5.5 years to see if it safely prevents bleeding episodes. The goal is to provide a…

This study follows 250 people with hemophilia A who are taking efanesoctocog alfa to prevent bleeding. Researchers want to see how well it protects joints from bleeds over time in everyday life. Participants will be observed for several years to track bleeding rates and treatment…

This program provides access to an experimental drug, AOC 1044, for people with Duchenne muscular dystrophy (DMD) whose genetic mutation can be treated by skipping exon 44. The goal is to help control the disease and improve muscle function. Participants must be at least 2 years …

This study gives people with moderate or severe hemophilia A who finished a previous trial continued access to the drug efanesoctocog alfa. The drug is a lab-made clotting factor that helps prevent bleeding episodes. Researchers will monitor safety and how well it controls bleedi…

This phase 3 trial is testing a drug called fitusiran in about 85 boys aged 1 to under 12 with severe hemophilia A or B, including those with inhibitors that make standard treatments less effective. The drug is given as a regular shot under the skin to help prevent bleeding episo…

This study is for adults with recurrent glioblastoma, an aggressive brain cancer. It tests whether adding a precise type of radiation (stereotactic radiosurgery guided by a special PET scan) to a device that delivers electric fields to the brain (TTFields) helps people live longe…

This phase 3 trial tests a new drug called FRSW107, a lab-made clotting factor VIII fused with a protein that helps it last longer in the body. The study enrolls males aged 12 to 65 with severe hemophilia A who have had at least 150 prior exposure days to factor VIII products. Pa…

This early-stage trial tests a gene therapy for people with hemophilia A, a bleeding disorder. The treatment uses a modified virus to deliver a working gene into the patient's own stem cells, which are then infused back. The goal is to help the body produce clotting factor VIII, …

This study tests a new gene therapy called SPK-8011QQ in 5 adult men with severe or moderately severe hemophilia A. The goal is to see if it is safe and tolerable. Participants receive a one-time intravenous dose, and researchers monitor for side effects and lab changes.

This program provides concizumab, a daily injection under the skin, for free to people with congenital hemophilia who need better treatment. Participants will be monitored for safety and how well the medicine works over several years. The program is for those with severe hemophil…

This study tests an experimental injection called SR604 in 76 adults with hemophilia A, B, or congenital factor VII deficiency. The goal is to see if it is safe and can reduce bleeding episodes. Participants will receive either a single dose or multiple doses, and researchers wil…

This Phase 3 trial tests a new drug called NXT007 (Zemocimig) against standard Factor VIII treatment to prevent bleeding in people with severe or moderate hemophilia A who do not have inhibitors. About 126 participants aged 12 and older will receive either NXT007 as a shot under …

This study compares a new drug, NXT007, to an existing one (emicizumab) for preventing bleeding episodes in people aged 12 and older with hemophilia A. Participants may have severe, moderate, or mild disease, with or without factor VIII inhibitors. The goal is to see if NXT007 is…

This study tests a new drug, NXT007, in people with severe or moderate hemophilia A. The drug is given as a shot under the skin, first every two weeks, then every four weeks. The goal is to see if it is safe and helps control bleeding. About 60 adults, teens, and children will ta…

This study looks at whether it is safe for males aged 12 and older with severe hemophilia A to switch from their current medicine (emicizumab) to a new one called fitusiran. About 20 participants will be followed for up to 28 months to check for side effects and how well the new …

This early-stage study tests a new medicine called marstacimab in people with severe hemophilia A who want to switch from their current preventive treatment, emicizumab. The study includes 15 adolescents and adults who will receive weekly injections of marstacimab for 4 months. R…

This early-phase trial tests a new gene therapy called ASP2957 for X-linked myotubular myopathy (XLMTM), a rare muscle disease present at birth that often requires a ventilator to breathe. The therapy delivers a healthy copy of the MTM1 gene using a modified virus. Nine boys up t…

This study tests a new medicine called DYNE-251 in boys aged 4 to 18 with Duchenne muscular dystrophy (DMD) who can still walk. The goal is to see if it helps them move better and slows muscle damage. Participants will receive either the drug or a placebo every 4 weeks for about …

This study tests a one-time gene therapy called TSHA-102 in girls aged 2 to 4 with Rett syndrome, a severe genetic disorder. The therapy is given as a single injection into the spine. The main goal is to check if it is safe and tolerable, and to see early signs of whether it help…

This study tests a stem cell transplant for people with common variable immunodeficiency (CVID) and other immune disorders. The goal is to replace the faulty immune system with a healthy donor's stem cells. Participants are aged 5 to 40 and will receive a reduced-intensity transp…

This study tests whether a recombinant factor VIII product called Nuwiq can safely prevent bleeding during major surgery in people with severe hemophilia A who are already on emicizumab. About 28 male patients aged 12 and older will take part. The main goal is to see if the treat…

This study is testing a drug called Nuwiq, a lab-made clotting factor, to prevent excessive bleeding during major surgery in women and girls with hemophilia A. About 28 participants will receive Nuwiq around the time of their surgery. Researchers will check if the drug successful…

This study tests a new medicine called marstacimab in children aged 1 to 17 with severe hemophilia A or B. The medicine is given as a weekly shot under the skin to prevent bleeding episodes. Researchers will compare how well it works to the children's own past year of standard tr…

This program offers early access to tiratricol, a thyroid hormone-like drug, for people with Allan-Herndon-Dudley syndrome (AHDS), a rare genetic condition that affects brain development and movement. Patients must have a confirmed genetic diagnosis and be considered likely to be…

This study tests a gene therapy called ATSN-201 in males aged 6 and older with X-linked retinoschisis, a genetic eye condition that leads to vision loss. The therapy delivers a working copy of the RS1 gene to the retina. The trial has three parts: first, finding the right dose; s…

This phase 3 study is testing whether a low, personalized dose of FEIBA (aPCC) can safely control bleeding in children and adults with hemophilia A who have inhibitors and are already taking emicizumab. The study will measure how well the blood clots after FEIBA is given and trac…

This registry follows 100 adults and teens with hemophilia A or B who are prescribed marstacimab, a once-weekly shot under the skin. The main goals are to see if patients prefer this shot over IV treatments and to measure treatment burden after 6 months. Researchers will also tra…

This study tests an experimental oral medicine called Inno8 in 30 adults with hemophilia A. The goal is to see if it is safe and how the body processes it. Participants will take multiple doses over about 11 weeks. If successful, Inno8 could offer a more convenient way to control…

This Phase 3 trial is testing STSP-0601, an injectable drug, to control bleeding episodes in people with hemophilia A or B who have developed inhibitors (antibodies that block standard treatment). The study will enroll 40 participants aged 12 to 70 and measure how well the drug s…

This Phase 3 study is testing a drug called KN057, given as a weekly injection under the skin, to prevent bleeding in people with hemophilia A or B (with or without inhibitors). The trial will enroll 70 males aged 12 to 65 and will monitor safety and how well the drug works over …

This study looks at whether a treatment called immune tolerance induction (ITI) can help people with haemophilia A who have developed inhibitors—antibodies that block standard clotting factor therapy. Researchers will give high doses of individualized factor VIII concentrates to …

This study tests a one-time gene therapy called ECUR-506 in baby boys under 9 months old with a severe form of OTC deficiency, a genetic disorder that prevents the body from breaking down ammonia. The goal is to see if the treatment is safe and can reduce dangerous ammonia levels…

This study tests whether emicizumab (Hemlibra), a medicine given as a shot under the skin, can safely prevent bleeding in people with severe von Willebrand disease (VWD) or combined VWD/hemophilia A. About 40 participants of any age (including infants) will receive the drug and b…

This study tests whether Yiyuancong, a traditional Chinese medicine made from food-like ingredients, can help people with sudden hearing loss. About 128 adults aged 18-60 will take the formula for 1-2 months, and their hearing will be measured with standard tests. The goal is to …

This early-stage study is testing whether quercetin, a natural antioxidant found in foods, is safe and can reduce inflammation in male patients with XIAP deficiency, a rare genetic immune disorder. Twelve participants will take oral quercetin daily. The main goals are to check fo…

This study tests a one-time gene therapy for a single person with X-linked Hyper-IgM syndrome, a rare immune disorder caused by a faulty CD40L gene. The participant's own stem cells and T cells are collected, edited in a lab to fix the gene mutation, and then infused back after c…

This study tests a new drug called ION440 in 48 people with MECP2 duplication syndrome, a rare genetic condition that causes intellectual disability and seizures. The drug is given via a spinal injection to see if it is safe and how the body processes it. Some participants will r…

This trial tests a one-time gene therapy called BBM-H803 for adults with severe hemophilia A. The treatment uses a harmless virus to deliver a working gene to the liver, so the body can produce its own clotting factor VIII. The study involves 55 participants and will check safety…

This early-stage trial is testing whether a combination of two natural substances, deoxycytidine and deoxythymidine, is safe for people with telomere biology disorders. These rare genetic conditions cause premature aging, bone marrow failure, and lung scarring. Up to 36 participa…

This study is testing a drug called SCT800, a lab-made clotting factor, to prevent bleeding episodes in 36 boys with severe hemophilia A who have never been treated before. Participants receive regular infusions of SCT800, and researchers will monitor how many bleeding events occ…

This study tests a medicine called prothrombin complex concentrate (PCC) to stop bleeding episodes in people with hemophilia A who have developed inhibitors (antibodies that block standard treatment). Thirty participants aged 12 to 65 will receive PCC on-demand during bleeding, w…

This study tracks 50 children and adults with non-malignant disorders like immune deficiencies and anemias who receive a stem cell transplant after a reduced-intensity chemotherapy regimen. The goal is to see if this approach improves survival and reduces severe graft-versus-host…

This study is testing the safety of a drug called SEVENFACT, a clotting factor made from the milk of genetically modified rabbits, in people aged 12 and older with hemophilia A or B who have inhibitors. The drug is already approved for treating bleeding episodes, and this trial w…

This study tests a one-time gene therapy called TSHA-102 in females aged 6 to under 22 with classic Rett syndrome. The goal is to see if it is safe and can help them regain or gain new developmental skills like walking or talking. Participants receive the therapy through a spinal…

This study is testing a less intense chemotherapy and radiation regimen before a stem cell transplant for children and young adults up to age 55 with non-cancerous blood disorders like immune deficiencies, anemias, and metabolic diseases. The goal is to see if this gentler prepar…

This trial tests a drug called DITPA in male infants with MCT8 deficiency, a rare genetic disorder that causes severe intellectual disability and movement problems. The drug aims to improve thyroid hormone function in the brain. Only infants whose families have a history of the c…

This study tests a single-dose gene therapy called GS1191-0445 in 50 Chinese men with hemophilia A. The treatment uses a harmless virus to deliver a working gene to the liver, helping the body produce its own clotting factor. The goal is to reduce bleeding episodes and the need f…

This study is for people with erythropoietic protoporphyria (EPP) or X-linked protoporphyria (XLP), rare conditions that cause severe pain and skin reactions to sunlight. The purpose is to check the long-term safety of an oral medication called dersimelagon. About 301 participant…

This phase 2 trial is testing a stem cell transplant using a milder chemotherapy regimen to treat people with severe immune deficiencies and inherited bone marrow failure. The goal is to see if donor cells can safely take over and rebuild a healthy immune system. Up to 27 partici…

This program offers extra stem cells from a half-matched family donor to patients who are getting a cord blood transplant for serious blood cancers or immune disorders. The goal is to help the bone marrow recover more quickly while the cord blood cells take over permanently. It i…

This Phase 3 study tests whether the drug leriglitazone can help adult men with cerebral adrenoleukodystrophy (cALD), a rare and serious brain disease. The main goal is to see if the drug delays death or the need for permanent breathing support compared to a placebo. About 40 men…

This study tests whether a once-weekly infusion of efanesoctocog alfa can improve joint swelling (synovial hypertrophy) in people with moderate to severe hemophilia A. Researchers will use ultrasound to measure changes in joint health over 12 months. The trial enrolls 35 particip…

This study tests a new drug called KK8123 for adults with X-linked hypophosphatemia (XLH), a rare genetic condition that causes low phosphate levels and bone problems. The trial has two parts: first, finding the right dose, then checking safety and how well it works over time. Ab…

This study in Taiwan will follow about 100 people with moderate to severe hemophilia A who are already taking efanesoctocog alfa (a clotting factor) as part of their routine care. Researchers will track joint health, bleeding rates, and safety over up to 5 years using medical rec…

This trial tests a gene therapy for X-linked adrenoleukodystrophy (X-ALD), a rare genetic disease that damages the brain. The therapy uses a modified virus to deliver a working copy of the faulty gene directly into the spinal fluid and bloodstream. Up to 30 patients aged 1 year a…

This early-stage trial tests whether adding special cells (DUOC-01) into the spinal fluid is safe for children with inherited metabolic diseases that damage the brain. Participants are ages 1 week to 21 years and are already receiving a standard umbilical cord blood transplant. T…

This study is testing a new blood test that can diagnose single-gene disorders in unborn babies using a sample from the mother. The test looks at fetal DNA found in the mother's blood, which is safer than traditional invasive methods that carry a small risk of miscarriage. Resear…

This study tests whether acetylcysteine, a drug often used for other purposes, can prevent hearing loss caused by cisplatin chemotherapy. About 40 adults receiving high-dose cisplatin will get either acetylcysteine or a placebo after each chemo session. Researchers will measure h…

This study tests a new medicine called CTH120 in 30 adult men with Fragile X syndrome. The main goal is to see if the drug is safe and tolerable, while also checking if it helps improve symptoms. Participants will receive the drug and be monitored closely for side effects and cha…

This study tests whether a non-invasive light therapy called photobiomodulation can reduce pain and swelling in the knees of children with hemophilia who have joint bleeding. Twenty-four boys and girls aged 9 to 14 will receive the light treatment alongside standard care. Researc…

This study is testing whether changing the low-frequency settings on a cochlear implant can improve hearing for people who are deaf in one ear but have normal hearing in the other. Twenty-two adults will try four different sound maps during their first month after implant activat…

This study tests an oral medicine called bionetide in 210 girls and women with Rett syndrome, a rare genetic disorder. The goal is to see if bionetide improves behavior and communication compared to a placebo over 12 weeks. Participants must be 5 to 20 years old and have a confir…

This study collects blood stem cells and immune cells from healthy volunteers and patients with primary immune deficiencies or blood disorders. The cells are used in the lab to develop new gene and cell therapies. Up to 850 adults aged 18-70 will participate. The goal is to advan…

This study creates a large registry of people with Rett syndrome, a rare genetic disorder that causes severe intellectual and physical disabilities. Researchers will collect information from doctors and caregivers to understand how the disease progresses over time. The goal is to…

This study follows about 50 boys under 18 with X-linked myotubular myopathy (XLMTM), a rare genetic muscle condition, to see how often they develop liver problems like cholestasis. No drugs are given—researchers simply collect health data, including liver scans, over one year. Th…

This observational study follows 150 people with MEHMO syndrome or related conditions to better understand how the disease progresses. Researchers will collect medical history, imaging, and lab samples to find biological markers that could help monitor the disease. No treatment i…

This study looks at the tiny organisms living on our skin—like bacteria and fungi—and how they might differ in people with eczema (atopic dermatitis). Researchers will collect skin samples from healthy volunteers and patients aged 2 to 40 with moderate to severe eczema, as well a…

This study monitors the safety of Jivi (damoctocog alfa pegol) in 20 Korean patients with hemophilia A who have used other treatments before. Researchers will collect data from routine clinic visits over about 8 months per participant, looking for any medical problems. No extra t…

This study aims to collect DNA samples and detailed eye exam data from 1,000 people with rare inherited eye diseases like aniridia, Best disease, and albinism. Participants provide a saliva or blood sample and share their eye health records. The goal is to expand a research repos…

This natural history study is observing up to 250 people with Smith-Lemli-Opitz syndrome and related cholesterol disorders, as well as their relatives. Researchers will track symptoms, development, and lab results over several years to find better ways to measure disease progress…

This study analyzes dried blood spots from 630 newborns to find protein and RNA markers that could predict which babies with congenital CMV will develop hearing loss or other problems. Researchers will compare samples from infected babies who had complications, those who did not,…

This study is observing how well three Factor VIII concentrates (Nuwiq, Octanate, Wilate) work in real-world settings for people with severe hemophilia A who have had little or no prior treatment. Researchers will track bleeding rates and side effects in about 200 participants of…

This study looks at how long-term phosphate therapy affects the kidneys, blood vessels, and heart in people with two rare bone disorders: X-linked hypophosphatemia (XLH) and hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Researchers will measure hormone levels an…

This study follows 173 people with hemophilia A or B who previously received a single-dose gene therapy in a Pfizer trial. Researchers will track bleeding episodes, clotting factor levels, and any long-term side effects like blood clots or liver issues. The goal is to understand …

This study uses brain MRI scans to look for tiny old bleeds (microbleeds) in 200 adults with severe hemophilia or von Willebrand disease. Researchers want to see how common these microbleeds are and whether they are linked to memory or thinking difficulties. Participants will als…

This registry collects information from people with inherited retinal diseases, like retinitis pigmentosa and Stargardt disease. Participants share their symptoms, family history, and genetic test results online. The goal is to help researchers understand these rare diseases and …

This study is testing a new, non-invasive method to predict bleeding risk in people with von Willebrand disease and other inherited bleeding disorders. Researchers will use a special microscope to look at tiny blood vessels under the tongue. The goal is to see if the density of t…

XLH is a rare genetic condition that causes low phosphate levels, leading to weak bones and pain. Burosumab is a standard treatment, but the best starting dose is still unclear. This study will review the medical records of 120 children across England to see if a lower dose (unde…

This study is a national registry for people with adrenoleukodystrophy (ALD), a rare genetic disorder. Researchers will collect medical records and survey data from up to 1,000 patients and their families over time to understand how the disease progresses. The goal is to find bet…

This observational study is gathering information on how erythropoietic protoporphyria (EPP) and X-linked porphyria (XLP) affect people aged 12 and older. Over 6 months, researchers will track symptoms, light exposure, and blood levels of protoporphyrin IX (PPIX) in 50 participan…

This study looks at whether ultrasound and other imaging can find hidden joint changes in people with hemophilia who have no obvious symptoms. Researchers will follow 46 patients for up to 12 weeks, using scans and physical exams to see if these hidden changes are active or inact…

This study uses a special camera called an adaptive optics scanning laser ophthalmoscope to take incredibly detailed pictures of the retina, the light-sensitive layer at the back of the eye. Researchers will compare images from healthy people and those with eye diseases like Star…

This study is a large registry that collects health information from up to 200,000 people with blood disorders such as hemophilia, thrombosis, and sickle cell disease. Participants are seen at Hemophilia Treatment Centers across the U.S. The goal is to gather real-world data to h…

This study looks at 36 adults with severe hemophilia A to understand how joint health, pain, balance, and falls impact their quality of life. Researchers will measure joint damage, balance using a special platform, pain levels, and fall history. The goal is to find which factors …

This study is collecting blood and other samples from 5,000 children and young adults (under 21) who are already taking certain medications as part of their regular care. The goal is to understand how these drugs move through and affect children's bodies, so doctors can prescribe…

This study enrolls 25 people with severe retinal diseases like retinitis pigmentosa and Stargardt disease to test new ways of measuring visual function. Researchers will evaluate how well participants can perform various vision tests, such as navigating obstacles or detecting lig…

This study looks at how well hip, knee, shoulder, and other joint replacement surgeries work in adults with inherited bleeding disorders like hemophilia. Researchers will collect information from medical records and follow patients over time to understand risks, complications, an…

This research study at Boston Children's Hospital is looking at the genes and proteins involved in congenital myopathies—rare muscle diseases that are present from birth. Researchers will analyze DNA from up to 4,000 participants, including patients and their family members, to f…

This study aims to create a reliable lab test to monitor how well anti-TFPI antibodies work in people with severe hemophilia. Researchers will take a single blood sample from 11 patients already on anti-TFPI therapy and test it in the lab. The goal is to better predict and manage…

This study looks at why people with hemophilia (a bleeding disorder) are less likely to die from heart disease. Researchers will use a new, detailed CT scanner to compare heart artery health in 80 men aged 45+ with hemophilia to similar men without it. The goal is to understand h…

This study looks at how nerves work in people with Charcot-Marie-Tooth disease and other nerve disorders like CIDP. Researchers will use special electrical tests and ultrasound to measure nerve and muscle changes. The goal is to better understand these conditions, not to test a n…

This study follows 500 mother-child pairs where the mother has a severe hemophilia A gene. It aims to understand bleeding risks during pregnancy and childbirth for mothers, and how children develop antibodies to factor VIII treatment. By observing families over time, researchers …

This study is creating a large database of people in China with various blood diseases, such as leukemia, multiple myeloma, and hemophilia. Researchers will collect information from medical records and follow participants over time to learn about disease patterns, treatments, and…

This study follows 1500 people with rare genetic brain disorders to learn how these diseases progress. Researchers measure thinking, movement, and daily living skills over time, and also look at brain scans and body fluids. The goal is to better understand the diseases and how tr…

This study looks at how short periods of high oxygen affect blood flow in the brains of ICU patients on breathing machines. Researchers will briefly increase the oxygen given through the ventilator and use ultrasound to monitor brain artery blood flow. The goal is to understand t…

This study aims to understand why people with Turner syndrome often lose their hearing. Researchers will look at genetic and epigenetic markers in 150 adults aged 18-60. Participants will have hearing, balance, blood, and imaging tests. The goal is to find new ways to treat or de…

This study is collecting long-term safety and effectiveness data on treatments for various blood disorders, including hemophilia, sickle cell disease, and clotting disorders. It aims to enroll 3000 people of any age with these conditions. Researchers will monitor side effects, co…

This study reports on a single adult with severe hemophilia A who is receiving long-term anticoagulation (blood thinners). The goal is to see if newer factor VIII therapies can maintain safe clotting levels while preventing dangerous clots. Only one participant is enrolled, so th…

This study follows 19 adults with hearing loss who already received a cochlear implant that releases a steroid to reduce inflammation. Researchers will check how well the implant works over 5 years by measuring electrical signals and tracking any side effects. The goal is to see …

This study explores whether a test that measures brain waves in response to visual images can be used in a new way for people with hearing loss. Researchers will compare these brain responses to standard hearing tests and thinking skills tests. The goal is to see if this test can…

This study collects medical information and biological samples (like blood or tissue) from up to 12,000 people with leukodystrophies—rare disorders that damage the brain's white matter. Researchers will use this data to find new genetic causes, develop biomarkers for future trial…

This study is a registry that tracks patients with blood diseases who receive stem cell transplants at a hospital on the Qinghai-Tibet Plateau. Researchers will collect information on recovery, complications, and costs over time. The goal is to understand how high altitude affect…

This study collects blood samples from 100 people with rare brain diseases like adrenoleukodystrophy and metachromatic leukodystrophy. Researchers will study immune cells called macrophages to see if they affect how the disease progresses. No treatment is given; the goal is to le…

This registry collects health data from 4,000 children with hemophilia A or B across Europe. Researchers track bleeding episodes, joint health, and antibody development to clotting factors. The goal is to understand long-term outcomes and improve treatment for this rare bleeding …

This study follows 120 men with hemophilia A who have developed inhibitors (antibodies that block standard treatment). Researchers will observe how doctors manage their condition using different therapies, including immune tolerance induction and newer drugs like emicizumab. The …

This study is testing new blood tests to see if they can better measure how well bleeding treatments work in people with haemophilia who have developed inhibitors (antibodies that block standard treatment). The researchers will take blood samples from 20 patients before and after…