Cerebrotendinous Xanthomatosis (CTX) Clinical Trials

CTX is caused by mutations in the CYP27A1 gene on chromosome 2, which encodes the mitochondrial enzyme sterol 27-hydroxylase. This enzyme normally catalyzes a key step in the conversion of cholesterol into bile acids, specifically chenodeoxycholic acid (CDCA), one of the two primary bile acids in humans. When the enzyme is deficient, the body cannot complete this pathway.

The most common symptoms of Cerebrotendinous Xanthomatosis include Chronic intractable diarrhea, often beginning in infancy or early childhood, Bilateral juvenile cataracts presenting in childhood or adolescence, Tendon xanthomas, typically on the Achilles tendons, appearing in adolescence or young adulthood, Progressive cerebellar ataxia and difficulty with balance, Pyramidal signs, peripheral neuropathy, and movement disorders, among others. Prevalence estimates vary widely by population. Genetic-frequency analyses suggest CTX may affect roughly 1 in 70,000 Americans, with somewhat higher rates in South and East Asian populations, but only around 300 individuals have been clinically identified worldwide, indicating substantial under-diagnosis. The average age at clinical diagnosis is 35 years, and the typical diagnostic delay from symptom onset is approximately 16 years.. Symptoms can range from mild to severe and may vary between individuals.

Trial Friend lists all active clinical trials for Cerebrotendinous Xanthomatosis from ClinicalTrials.gov, with eligibility criteria translated into plain English. Patients can filter by trial phase and recruitment status, search by location, and use the Match Me tool to score trials against their profile. On February 21, 2025, the FDA approved Ctexli (chenodiol) as the first therapy specifically indicated for CTX. The approved indication covers adults only; pediatric use remains off-label.

On February 21, 2025, the FDA approved Ctexli (chenodiol) as the first targeted therapy specifically for cerebrotendinous xanthomatosis, indicated in adults at 250 mg three times daily. Ctexli is purified chenodeoxycholic acid — the exact bile acid CTX patients cannot make on their own. Replacing it directly turns the blocked pathway back on and lowers cholestanol levels. The pivotal RESTORE trial was a 24-week study in which patients were randomly assigned to Ctexli or placebo and the medications were swapped halfway through; Ctexli significantly reduced cholestanol in the blood and 23S-pentol in the urine compared with placebo. Ctexli carries a warning for liver injury, so liver enzyme blood tests are required before starting and periodically during treatment. Pediatric use is not on the label yet, so use in children is considered off-label. Statins are sometimes added to address premature heart disease, though they do not fix the underlying enzyme problem. Mirum Pharmaceuticals operates a patient access program that helps uninsured and underinsured patients afford the drug.

Cerebrotendinous xanthomatosis (CTX) is caused by mutations in the CYP27A1 gene, which makes an enzyme called sterol 27-hydroxylase. This enzyme normally helps the body convert cholesterol into chenodeoxycholic acid (CDCA), one of the two main bile acids — substances your liver makes to help digest fat. When the enzyme is missing or broken, the body cannot finish making bile acids the right way. Building blocks back up, and a fat called cholestanol along with cholesterol itself collects in tissues throughout the body, especially the brain, spinal cord, peripheral nerves, tendons, the lens of the eye, and arteries. Over decades, those deposits damage the tissues, producing the classic CTX pattern: chronic stubborn diarrhea in infancy, juvenile cataracts (cloudy lenses in the eyes appearing in childhood or teens), tendon xanthomas (soft fatty growths most often noticed on the Achilles tendons in young adulthood), and progressive neurological problems including ataxia (loss of coordination), thinking and memory decline, peripheral nerve damage, and seizures in adulthood. Premature heart disease and weak bones are also common. The two diagnostic markers are elevated cholestanol in blood and a urinary chemical called 23S-pentol.

CYP27A1 gene sequencing is the definitive diagnostic test for cerebrotendinous xanthomatosis. More than 100 different disease-causing variants have been identified across all coding parts of the gene. Diagnosis is supported by elevated cholestanol in the blood (typically 5 to 10 times the normal range) and a characteristic urinary bile alcohol called 23S-pentol. Because CTX is autosomal recessive — meaning you need a defective copy from both parents to be affected — both parents are obligate carriers and siblings each have a 25 percent chance of being affected. Cascade testing (testing of close relatives once one family member is diagnosed) is critical because early treatment with bile acid replacement can stabilize or even prevent neurological problems that otherwise become permanent. Newborn screening pilot programs (ScreenPlus at Albert Einstein College of Medicine and Early Check at RTI International) are evaluating whether CTX should be added to routine state newborn screening panels. Labs offering CYP27A1 testing include GeneDx, Invitae, PreventionGenetics, Blueprint Genetics, and university metabolic disease labs. Genetic counseling is recommended for affected families.

Eligibility for Cerebrotendinous Xanthomatosis clinical trials depends on factors like age, diagnosis, treatment history, and overall health. Each trial sets its own inclusion and exclusion criteria. Trial Friend translates these requirements from medical language into plain English so patients can review them more easily. The Match Me tool can score your profile against active trials to help identify studies that may be a fit.

Participating in a Cerebrotendinous Xanthomatosis clinical trial typically involves scheduled visits, medical tests, and close monitoring by a research team. Depending on the study phase, you may receive an investigational treatment, a placebo, or the current standard of care. Trials may last from a few weeks to several years. Study participation is voluntary, and you can withdraw at any time.

Cerebrotendinous xanthomatosis clinical trial activity is limited because Ctexli has just been approved and the patient population is small (roughly 5,000 in the U.S., though many are still undiagnosed). Trials that exist focus on long-term natural history (the Myelin Disorders Biorepository at Children's Hospital of Philadelphia), pediatric chenodiol use to expand the on-label indication beyond adults, and newborn screening evaluation (the ScreenPlus and Early Check programs). Patients on prior chenodeoxycholic acid (whether from compounding pharmacies, Xenbilox imported from Europe, or other off-label use) typically need to document their treatment history rather than stop it. Statins, vitamin D, and calcium supplements are usually allowed and continued. Trial Friend's medication conflict checker scans each trial's exclusion criteria against chenodiol, statins, and other medications used to manage the systemic complications of CTX. The checker flags the specific drug, the trial's exclusion language, and a confidence level so you can discuss timing with your metabolic specialist or neurologist.

Key questions to ask your neurologist or metabolic specialist about CTX: Has CYP27A1 gene testing confirmed the diagnosis, and what are my current cholestanol and 23S-pentol levels — the two markers that should drop on Ctexli if it is working? On the FDA-required liver monitoring schedule, will my liver-function blood tests be checked at baseline, monthly for the first 3 months, then every 3 months after? My child is under 18 — can we use chenodiol off-label, since early treatment can prevent neurological damage that later becomes permanent? Should we add a statin for the premature heart disease and bone-density loss CTX causes, and which one avoids drug interactions with Ctexli? Should my siblings be tested too, given the 25 percent chance of being affected in this autosomal recessive disease (where you need a defective copy from both parents)?