High Dose Ascorbic Acid Treatment of CMT1A

NCT ID: NCT00484510

Last Updated: 2013-03-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-04-30
• Study Completion Date: 2012-12-31

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.

Conditions

Charcot-Marie-Tooth Disease, Type Ia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Ascorbic Acid

Group Type: EXPERIMENTAL

Ascorbic acid (Vitamin C)

Intervention Type: DRUG

Eight 500 mg capsules/day of ascorbic acid. Subjects will take four (4)capsules each morning and four (4) capsules each evening for 24 months. (Total 4 gr/day).

Placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Eight 500 mg capsules/day of placebo. Subjects will take four (4)capsules each morning and four (4) capsules each evening for 24 months.

Interventions

Ascorbic acid (Vitamin C)

Eight 500 mg capsules/day of ascorbic acid. Subjects will take four (4)capsules each morning and four (4) capsules each evening for 24 months. (Total 4 gr/day).

Intervention Type: DRUG

placebo

Eight 500 mg capsules/day of placebo. Subjects will take four (4)capsules each morning and four (4) capsules each evening for 24 months.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Muscular Dystrophy Association

OTHER

Sponsor Role: collaborator

Charcot-Marie-Tooth Association

OTHER

Sponsor Role: collaborator

Wayne State University

OTHER

Sponsor Role: lead

Responsible Party

Michael E. Shy, MD

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard A Lewis, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University, Dept. of Neurology

Locations

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

Countries

United States

References

Lewis RA, McDermott MP, Herrmann DN, Hoke A, Clawson LL, Siskind C, Feely SM, Miller LJ, Barohn RJ, Smith P, Luebbe E, Wu X, Shy ME; Muscle Study Group. High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A: results of a randomized, double-masked, controlled trial. JAMA Neurol. 2013 Aug;70(8):981-7. doi: 10.1001/jamaneurol.2013.3178.

Reference Type: DERIVED

PMID: 23797954 (View on PubMed)

Other Identifiers

MDA4193

Identifier Type: -

Identifier Source: secondary_id

HIC074406MP2F

Identifier Type: -

Identifier Source: org_study_id