Charcot-Marie-Tooth Disease, Type IaPhase 2/3NCT00484510
High Dose Ascorbic Acid Treatment of CMT1A
A Phase 2/3 study testing Ascorbic acid (Vitamin C) in people with Charcot-Marie-Tooth Disease, Type Ia, run by Wayne State University at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 13 to 70 years
- Conditions the study is for
- Charcot-Marie-Tooth Disease, Type Ia
- What is being tested?
- Ascorbic acid (Vitamin C)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 110 participants
- Where
- 3 sitesUnited States
- Study dates
- Apr 2007to Dec 2012
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 13 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Johns Hopkins University, Dept of Neurology
Baltimore, Maryland, 21287
Wayne State University, Dept of Neurology
Detroit, Michigan, 48201
University of Rochester Medical Center, Dept of Neurology
Rochester, New York, 14642
About this study
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.
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.
Read the 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
- Being tested
- Ascorbic acid (Vitamin C), placebo
- Keywords
- Ascorbic Acid, Vitamin C, Charcot Marie Tooth, CMT, CMT1a
- Medical subject headings
- Charcot-Marie-Tooth Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ascorbic acid (Vitamin C)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).
placeboDrug
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 group | Role | What they receive |
|---|---|---|
| Ascorbic Acid | Experimental | Not described Receives: Drug: Ascorbic acid (Vitamin C) |
| Placebo | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean change in the CMT Neuropathy Scale following high dose ascorbic acid ingestion, assessed at baseline and every 6 months throughout the trial.
Measured: 25 months per subject from baseline to completion.
Secondary outcomes (1)
Evaluation of PMP22 mRNA levels of myelinated peripheral nerve fibers.
Measured: Baseline and Month 24.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2007 (estimated)
- Study startApr 2007
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Charcot-Marie-Tooth Disease, Type IaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wayne State University
- Sponsor type
- University, hospital or other
- Collaborators
- Muscular Dystrophy Association, Charcot-Marie-Tooth Association
- Responsible party
- Principal investigator, Michael E. Shy, MD, Wayne State University
- Investigators
- Richard A Lewis, MD, Principal investigator, Wayne State University, Dept. of Neurology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00484510
- Sponsor's protocol ID
- HIC074406MP2F
- Other IDs
- MDA4193
- Status last verified
- Mar 2013
- First submitted
- 8 Jun 2007
- Last updated
- 6 Mar 2013
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 23797954
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT00484510
- Acronym / sponsor ID
- HIC074406MP2F
- Conditions
- Charcot-Marie-Tooth Disease, Type Ia
- Keywords
- Ascorbic Acid, Vitamin C, Charcot Marie Tooth, CMT, CMT1a
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Wayne State UniversityUniversity, hospital or other
- Collaborators
- Muscular Dystrophy Association, Charcot-Marie-Tooth Association
- Study start
- Apr 2007
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 11 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ascorbic Acid | Experimental | Drug: Ascorbic acid (Vitamin C) |
| Placebo | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 13 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Ascorbic Acid |
| placeboEight 500 mg capsules/day of placebo. Subjects will take four (4)capsules each morning and four (4) capsules each evening for 24 months. | Drug | Placebo |
Primary outcome
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.
1 secondary outcome
Evaluation of PMP22 mRNA levels of myelinated peripheral nerve fibers.
Time frame: Baseline and Month 24.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2013.
- Derived from this study: PubMed 23797954Lewis 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard A Lewis, MD principal investigator
Wayne State University, Dept. of Neurology
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Ascorbic acid (Vitamin C) in people with Charcot-Marie-Tooth Disease, Type Ia, run by Wayne State University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Mar 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00484510, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2013.