High Dose Ascorbic Acid Treatment of CMT1A

• ClinicalTrials.gov Identifier: NCT00484510
• Recruitment Status: Completed
• First Posted: June 11, 2007
• Last Update Posted: March 6, 2013
• Sponsor: Wayne State University
• Collaborators: Muscular Dystrophy Association; Charcot-Marie-Tooth Association
• Information provided by (Responsible Party): Michael E. Shy, MD, Wayne State University

Tracking Information

• First Submitted Date: June 8, 2007
• First Posted Date: June 11, 2007
• Last Update Posted Date: March 6, 2013
• Study Start Date: April 2007
• Actual Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 8, 2007): Mean change in the CMT Neuropathy Scale following high dose ascorbic acid ingestion, assessed at baseline and every 6 months throughout the trial. [ Time Frame: 25 months per subject from baseline to completion. ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: June 8, 2007): Evaluation of PMP22 mRNA levels of myelinated peripheral nerve fibers. [ Time Frame: Baseline and Month 24. ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: High Dose Ascorbic Acid Treatment of CMT1A
• Official Title: A Randomized, Placebo-controlled, Double Masked 120 Subject "Futility Design" Clinical Trial of Ascorbic Acid Treatment of Charcot Marie Tooth Disease Type 1A.
• 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.
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Charcot-Marie-Tooth Disease, Type Ia

Intervention

• Drug: 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).
• 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.

Study Arms

• Experimental: Ascorbic Acid
  Intervention: Drug: Ascorbic acid (Vitamin C)
• Placebo Comparator: Placebo
  Intervention: Drug: placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 4, 2013): 110
• Original Estimated Enrollment (submitted: June 8, 2007): 120
• Actual Study Completion Date: December 2012
• Actual Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 13 Years to 70 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00484510
• Other Study ID Numbers: HIC074406MP2F; MDA4193
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Michael E. Shy, MD, Wayne State University
• Original Responsible Party: Not Provided
• Current Study Sponsor: Wayne State University
• Original Study Sponsor: Same as current

Collaborators

• Muscular Dystrophy Association
• Charcot-Marie-Tooth Association

Investigators

• Principal Investigator: Richard A Lewis, MD; Wayne State University, Dept. of Neurology

• PRS Account: Wayne State University
• Verification Date: March 2013