MedPath

High Dose Ascorbic Acid Treatment of CMT1A

Phase 2
Completed
Conditions
Charcot-Marie-Tooth Disease, Type Ia
Interventions
Drug: Ascorbic acid (Vitamin C)
Drug: placebo
Registration Number
NCT00484510
Lead Sponsor
Wayne State University
Brief Summary

This study will look at the impact of ascorbic acid (Vitamin C) on the progression of disease in people with CMT1A as compared to volunteers receiving a placebo. This study will assess whether is it futile to proceed with a larger, longer-term, placebo-controlled study.

Detailed Description

Charcot Marie Tooth disease (CMT), or inherited peripheral neuropathies, are among the most frequent heritable disorders, affecting approximately 1 in 2500 people. The most frequent genetic form of CMT is CMT1A. CMT1A is caused by a 1.4 Mb duplication within chromosome 17p11.2 in the region containing the PMP22 gene. Most subjects with CMT1A have a "typical" phenotype characterized by onset in childhood or early adulthood, distal weakness, sensory loss, foot deformities and absent reflexes. How increased expression of PMP22 causes these disabilities is unknown but is currently being investigated in both animal and tissue culture systems. In this study, researchers will evaluate whether ascorbic acid (Vitamin C), administered orally, slows clinical progression of CMT1A and affects the PMP22 mRNA levels of myelinated peripheral nerve fibers obtained from biopsies of glabrous skin.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
110
Inclusion Criteria
  • The subject has CMT1A, defined by the duplication on chromosome 17p11.2 performed by either Pulse Field Gel Electrophoresis or Fluorescence In Situ Hybridization (FISH) by a CLIA certified laboratory, OR the subject has a first or second degree relative with a documented duplication performed by the above methods AND the subject has uniform motor conduction slowing of the median or ulnar nerve between 16 and 30 m/s.
  • The subject is between 13 and 70 years of age.
  • The subject, if 18 years or older, has signed the Informed Consent Form and agrees to follow the stipulations of the protocol.
  • If the subject is less than 18, his or her parents or guardians have signed the Informed Consent Form and agree to follow the stipulations of the protocol. The subject has also signed a written assent form.
Exclusion Criteria
  • A known neuropathy from another source (For example, diabetes, drug induced, alcohol, etc.)
  • The subject has ever received Vincristine.
  • The subject has a known allergy to ascorbic acid.
  • The subject has ever had kidney stones.
  • The subject has a known history of G6PD deficit.
  • The subject has a history of hemochromatosis.
  • The subject suffers from a serious illness or medical condition that is not stabilized or that could require hospitalization.
  • The subject has a high ascorbic acid level at screening.
  • The subject is pregnant or nursing.
  • The subject, in the opinion of the investigator, is unlikely to comply with the study protocol or is unsuitable for any other reason.
  • The subject participates to another clinical trial or is still within a washout period of a previous clinical trial.
  • The subject is taking neurotoxic medications.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Ascorbic AcidAscorbic acid (Vitamin C)-
Placeboplacebo-
Primary Outcome Measures
NameTimeMethod
Mean change in the CMT Neuropathy Scale following high dose ascorbic acid ingestion, assessed at baseline and every 6 months throughout the trial.25 months per subject from baseline to completion.
Secondary Outcome Measures
NameTimeMethod
Evaluation of PMP22 mRNA levels of myelinated peripheral nerve fibers.Baseline and Month 24.

Trial Locations

Locations (3)

Johns Hopkins University, Dept of Neurology

🇺🇸

Baltimore, Maryland, United States

Wayne State University, Dept of Neurology

🇺🇸

Detroit, Michigan, United States

University of Rochester Medical Center, Dept of Neurology

🇺🇸

Rochester, New York, United States

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