Ascorbic Acid Treatment in CMT1A Trial (AATIC)

NCT00271635 | Completed Phase 2 DMC

• 1 other identifier: 04/320
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Charcot-Marie-Tooth type IA (CMT1A) is the most prevalent hereditary peripheral neuropathy. Demyelination of peripheral nerves is the hallmark of CMT1A. Ascorbic acid has been shown to have a favorable influence on myelination in in vitro studies and in a mouse model for CMT1A. We will study the efficacy and safety of ascorbic acid treatment in young patients with CMT1A.

Conditions

Charcot-Marie-Tooth Disease; Hereditary Motor and Sensory Neuropathies

Keywords

Charcot-Marie-Tooth Disease; Hereditary Motor and Sensory Neuropathies; Ascorbic Acid; Vitamin C

Outcome Measures

Primary Outcomes (1)

• Change in motor nerve conduction velocity of the median nerve after 1 year

  1 year

Secondary Outcomes (8)

• Change in minimal F response latency of the median nerve after 1 year

  1 year

• Changes in compound muscle action potential amplitude and area after 1 year

  1 year

• Change in motor unit number estimation of the abductor pollicis brevis muscle after 1 year

  1 year

• Changes in handgrip strength, strength of armflexors, foot dorsiflexors, knee extensors and hip flexors after 1 year

  1 year

• Change in overall disability sum score after 1 year

  1 year

Study Arms (2)

1

EXPERIMENTAL

Ascorbic acid

Drug: ascorbic acid

2

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Placebo DRUG

Placebo 4 capsules b.i.d. during 1 year

2

ascorbic acid DRUG

Ascorbic acid 1000 mg (4 capsules of 250 mg) b.i.d. during 1 year

Also known as: Vitamin C

1

Eligibility Criteria

• Age: 12 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• DNA-proven CMT1A patients
• Age 12-25 years
• CMT 1A patients with symptomatology defined as muscle weakness in at least foot dorsiflexion

You may not qualify if:

• Due to possible influence on severity of the neuropathy:
• Known other disease that may cause a neuropathy, that may decrease mobility, or that may lead to severe disability or death in a short time
• Medication that may cause a neuropathy
• Chronic alcohol abuse
• Due to study medication (ascorbic acid):
• Regular use of vitamin C
• Clinical or echographic signs of nephrolithiasis
• Reduced glomerular filtration rate
• Iron overload
• No regular dental control at the dentist
• Pregnancy or active pregnancy wish for women
• Due to study design and primary outcome:
• Not signing the informed consent
• Psychiatric co-morbidity which may influence compliance
• Not being comfortable during nerve conduction studies of the median nerve

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Department of Neurology Academic Medical Center University of Amsterdam

Amsterdam, P.O.Box 22660, 1100 DD, Netherlands

Location

Related Publications (3)

• Passage E, Norreel JC, Noack-Fraissignes P, Sanguedolce V, Pizant J, Thirion X, Robaglia-Schlupp A, Pellissier JF, Fontes M. Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease. Nat Med. 2004 Apr;10(4):396-401. doi: 10.1038/nm1023. Epub 2004 Mar 21.

  PMID: 15034573 BACKGROUND

• Verhamme C, van Schaik IN, Koelman JH, de Haan RJ, Vermeulen M, de Visser M. Clinical disease severity and axonal dysfunction in hereditary motor and sensory neuropathy Ia. J Neurol. 2004 Dec;251(12):1491-7. doi: 10.1007/s00415-004-0578-x.

  PMID: 15645349 BACKGROUND

• Verhamme C, de Haan RJ, Vermeulen M, Baas F, de Visser M, van Schaik IN. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial. BMC Med. 2009 Nov 12;7:70. doi: 10.1186/1741-7015-7-70.

  PMID: 19909499 DERIVED

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy

Interventions

Ascorbic Acid

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates

Study Officials

• C. Verhamme, MD

  Department of Neurology, Academic Medical Center, University of Amsterdam

  PRINCIPAL INVESTIGATOR

• M. Vermeulen, MD, PhD

  Department of Neurology, Academic Medical Center, University of Amsterdam

  PRINCIPAL INVESTIGATOR

• F. Baas, MD, PhD

  Department of Neurology, Academic Medical Center, University of Amsterdam

  PRINCIPAL INVESTIGATOR

• R. de Haan, MD, PhD

  Department of Neurology, Academic Medical Center, University of Amsterdam

  PRINCIPAL INVESTIGATOR

• M. de Visser, MD, PhD

  Department of Neurology, Academic Medical Center, University of Amsterdam

  PRINCIPAL INVESTIGATOR

• I. N van Schaik, MD, PhD

  Department of Neurology, Academic Medical Center, University of Amsterdam

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 3, 2006
• First Posted: January 4, 2006
• Study Start: January 1, 2006
• Primary Completion: July 1, 2007
• Study Completion: July 1, 2007
• Last Updated: July 4, 2008

Record last verified: 2008-07

Locations

NL (1)