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This is a Phase 2a double-blind, placebo-controlled study with two dose levels of A0001 given twice daily for 28 days. Potential subjects will be screened first to determine eligibility, after which they will be randomized to receive either a high dose of A0001, a low dose of A0001 or placebo for 28 days.
Eligible subjects will return within 21 days of screening for the baseline visit and randomization to one of three potential treatments. The subjects will be required to take 3 capsules of study medication in the morning with a morning meal and 3 capsules of study medication at night with an evening meal for 28 days. Additional visits to the clinic are planned for Day 14 and Day 28, at which time a number of clinical and biochemical assessments will be done.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Low Dose | Experimental | A0001 (0.5 g BID) |
|
| High Dose | Experimental | A0001 (0.75 g BID) |
|
| Placebo | Placebo Comparator | Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| alpha-tocopherolquinone (A0001) | Drug | 28 days of low dose (1.0 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Disposition Index of Glucose Regulation, determined by Frequent Sampling IV Glucose Tolerance Test | Baseline, Day 14 and Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Sensitivity index (SI) calculated from IVGTT | Baseline, Day 14 and Day 28 | |
| Glucose effectiveness (SG) calculated from IVGTT | Baseline, Day 14 and Day 28 | |
| AIRg for glucose and insulin during IVGTT |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Lynch, MD, PhD | Children's Hospital of Philadelphia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22744651 | Derived | Lynch DR, Willi SM, Wilson RB, Cotticelli MG, Brigatti KW, Deutsch EC, Kucheruk O, Shrader W, Rioux P, Miller G, Hawi A, Sciascia T. A0001 in Friedreich ataxia: biochemical characterization and effects in a clinical trial. Mov Disord. 2012 Jul;27(8):1026-33. doi: 10.1002/mds.25058. Epub 2012 Jun 28. | |
| 22633670 | Derived |
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| ID | Term |
|---|---|
| D005621 | Friedreich Ataxia |
| ID | Term |
|---|---|
| D013132 | Spinocerebellar Degenerations |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| C002421 | tocopherylquinone |
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| alpha-tocopherolquinone (A0001) | Drug | 28 days of high dose (1.5 g total daily dose) oral A0001 capsules. Treatment taken twice daily with meals. |
|
| placebo | Drug | 28 days of placebo oral capsules. Treatment taken twice daily with meals. |
|
| Baseline, Day 14 and Day 28 |
| Fasting Glucose, Insulin and Lactate | Baseline, Day 14 and Day 28 |
| HbA1C | Baseline, Day 14 and Day 28 |
| Plasma 1,5-anhydroglucitol (1,5-AG) (Glycomark) | Baseline, Day 14 and Day28 |
| Specific Activity of Complex 1 in whole blood | Baseline, Day 14 and Day 28 |
| Timed 25 Foot Walk Test | Baseline and Day 28 |
| FARS/neurological exam | Baseline and Day 28 |
| 9-Hole Peg Test | Baseline, Day 14 and Day 28 |
| Vision Low Contrast Letter Acuity Test | Baseline and Day 28 |
| Global Impression of Clinical Severity | Baseline, Day 14 and Day 28 |
| Modified Fatigue Impact Scale | Baseline and Day 28 |
| Activities of Daily Living | Baseline and Day 28 |
| SF-36® | Baseline and Day 28 |
| Friedman LS, Schadt KA, Regner SR, Mark GE, Lin KY, Sciascia T, St John Sutton M, Willi S, Lynch DR. Elevation of serum cardiac troponin I in a cross-sectional cohort of asymptomatic subjects with Friedreich ataxia. Int J Cardiol. 2013 Aug 20;167(4):1622-4. doi: 10.1016/j.ijcard.2012.04.159. Epub 2012 May 26. |
| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028361 | Mitochondrial Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |