Clinical Research Directory

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.

Research of SORD-CMT Natural History and Epalrestat Treatment

Charcot-Marie-Tooth disease (CMT) is a group of the most common hereditary peripheral neuropathy with high clinical and genetic heterogeneity. Biallelic pathogenic variants in SORD gene leading to loss of function of SORD protein cause axonal degeneration. Current research suggests that SORD-CMT2 may be the most common subtype of AR-CMT2. The primary purpose of this study is to explore the natural history of SORD-CMT2 patients by detecting the ONLS scale score and serum sorbitol level changes at 6th, 12th, 24th, and 36th months and to evaluate the effectiveness and safety of epalrestat. Patients with strong treatment willingness and voluntary purchase of drugs are included in the epalrestat treatment group, and patients without drug treatment willingness are included in the control group. Patients in the drug treatment group take epalrestat (50 mg) orally three times daily. This study is expected to be carried out simultaneously in 5 hospitals in mainland China. About 30 SORD-CMT2 patients will be enrolled in this study, and the study period will be 36 months.