Clinical Research Directory

Tools for Therapeutic Evaluation in Charcot-Marie-Tooth Disease Type 1A: Outcome Measures and Biomarkers

This is a 2-year follow-up study of a cohort of 60 CMT1A patients. The objective is to identify markers allowing to better understand the phenotypic variability observed on patients with CMT1A, to identify predictive markers of the disease's progression and to provide validated measurement tools that can be used as outcome measures in future clinical trials.

Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease

This is a 2-year follow-up study of a cohort of 35 CMT1A patients and 20 healthy volunteers. The main objective is identifying prognostic markers for CMT1A using multi-omics analysis. The study is recruiting subjects between the ages of 10 and 30. The most common inherited neuropathy is Charcot-Marie-Tooth disease type 1A (CMT1A), caused by a duplication of the gene expressing PMP22. CMT1A patients develop symptoms in early childhood with variable progression and there is no established therapy until now. Therapy must start in childhood, before peripheral nerves degenerate. However, we lack easily obtainable biomarkers in early disease stages. In CMT-MODs, we will identify disease and prognostic biomarkers in young CMT1A patients.

Muscle MRI Fat Fraction Before Surgery to Predict Strength Recovery After Foot-Drop Surgery in Charcot-Marie-Tooth Disease

The purpose of this prospective observational cohort study is to determine whether the amount of fat inside the donor muscles before surgery, measured with a magnetic resonance imaging (MRI) technique called Dixon fat fraction (FF), can predict how much ankle dorsiflexion strength patients with Charcot-Marie-Tooth disease (CMT) recover after tibialis posterior tendon transfer surgery. CMT is an inherited nerve disease that weakens the feet and legs, causing foot drop and high-arched, inwardly turned feet. A common operation transfers the tibialis posterior tendon to the top of the foot to restore foot lifting; however, the transplanted muscle itself may be weakened by fatty degeneration, and surgeons currently have no objective way to know in advance how well the transferred muscle will work. We hypothesize that a lower preoperative fat fraction of the tibialis posterior (donor) muscle is associated with greater recovery of dorsiflexion strength after surgery. A total of 100 adults (18-55 years) with genetically confirmed CMT types 1A, 1X or 2A who are scheduled for individualized foot surgery that includes tibialis posterior tendon transfer will be enrolled at 4 foot-and-ankle centers in China. Within 1 month before surgery, participants will undergo a lower-leg MRI with a Dixon sequence to measure the fat fraction of 11 calf muscles. Participants will then be followed for 5 years (3 and 6 months, and 1, 2, 3, 4 and 5 years after surgery). At every visit, ankle dorsiflexion strength will be measured with a hand-held dynamometer and normalized to body weight (newtons per kilogram); walking ability (1-minute walk distance, 10-meter walking speed), ankle range of motion, clinical severity scales (CMTES, Walk-12, FADI, SF-12) and CMT-related symptoms (pain, fatigue, cramps, balance and falls, sensory loss, hand function, brace use, calluses, mood) will also be assessed. Surgical details of every additional procedure will be recorded. The primary analysis will correlate preoperative tibialis posterior fat fraction with the change in dorsiflexion strength at each time point (principal endpoint: 12 months), and will test whether fat fraction independently predicts strength recovery in a multivariable regression model. If confirmed, preoperative muscle fat fraction could become an objective, readily available imaging marker to help surgeons select patients, choose between tendon transfer alternatives, and counsel patients about expected outcomes.

Clinical Trial Evaluating the Impact of an Intensive Rehabilitation Program Combined With Tendon Vibratory Stimulation on Functional Balance in Individuals With Charcot-Marie-Tooth Disease Type 1A

Charcot-Marie-Tooth (CMT) disease is caused by a genetic abnormality involving the PMP22 gene, resulting in demyelination of the peripheral nerves. Demyelination leads to sensorimotor impairment and causes progressive muscle weakness and tendon contractures, initially affecting the lower limbs. Consequently, individuals with CMT experience balance impairments and gait disturbances, including ankle instability, foot drop, and postural instability, which lead to frequent falls and reduced quality of life. Currently, there is no disease-modifying treatment for CMT. Several rehabilitation approaches have been proposed, including endurance training and muscle strengthening programs, to improve independence in activities of daily living. However, rehabilitation practices for individuals with CMT remain poorly standardized, and there is still a lack of clearly defined rehabilitation protocols, despite broad agreement among healthcare professionals regarding their potential benefits. More recently, noninvasive focal tendon vibration has been investigated in several neurological disorders to improve sensory function, balance, and motor performance. Previous studies suggest that mechanical vibratory stimulation applied to the quadriceps tendon may induce sustained improvements in postural control and lower-limb muscle strength. The present study aims to evaluate a rehabilitation program combined with tendon vibratory stimulation. The objective is to compare the effectiveness of a short-term (2-week), intensive multidisciplinary rehabilitation program focused on balance with different types of focal tendon vibration, in order to better address balance impairments and their associated complications in individuals with Charcot-Marie-Tooth disease.

Evaluate the Safety and Efficacy of EN001 in Patients With Charcot-Marie-Tooth Disease Type 1A(CMT1A) (Phase 1b: Open-label, Dose-escalation, Single-center; Phase 2a: Randomized, Double-blind, Placebo-controlled, Multicenter)

A Phase 1b/2a Clinical Trial to Evaluate the Safety and Efficacy of EN001 in Patients with Charcot-Marie-Tooth Disease type 1A(CMT1A) (Phase 1b: Open-label, Dose-escalation, Single-center; Phase 2a: Randomized, Double-blind, Placebo-controlled, Multicenter)