- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01537549
Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy
An Open-label Trial of Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy (PSP): Effect Upon Oxidative Damage and Mitochondrial Biomarkers
Studies have shown that alpha-lipoic acid and L-acetyl carnitine may have some neuroprotective activities and it is hoped that they could be helpful for people with neurodegenerative illnesses such as progressive supranuclear palsy (PSP).
The purpose of this study is to find out whether the nutritional supplement alpha-lipoic acid/L-acetyl carnitine is safe and well-tolerated in individuals with PSP when given daily, and whether it affects their well-being, brain scan measurements and blood tests that measure the energy metabolism in cells.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Multiple lines of evidence support mitochondrial dysfunction and oxidative stress playing a role in the pathogenesis of atypical Parkinsonism, including PSP. Such dysfunction may well contribute to the tau pathology that is well-recognized in PSP, thus providing a link between the two processes. This pathway therefore represents an excellent potential target for novel therapeutic intervention in neurodegenerative disorders, and a number of well-tolerated and safe nutritional supplements have been identified that appear to augment mitochondrial function, and improve oxidative stress.
Alpha-lipoic acid and L-acetyl carnitine are two nutritional supplements that have received increasing attention as potential neuroprotective interventions in neurodegenerative and other disease states. Alpha-lipoic acid/L-acetyl carnitine had been demonstrated to improve learning in aged beagles over 2 months of administration, and showed a trend to improve cognitive function in a mouse model of Alzheimer's disease (human apoE4 transgene). Moreover, alpha-lipoic acid/L-acetyl carnitine was neuroprotective in a mouse model of Parkinson's disease (rotenone-induced parkinsonism), with effects including decreased oxidative stress, and increased mitochondrial biogenesis. In fibroblasts derived from individuals with Alzheimer's disease, alpha-lipoic acid/L-acetyl carnitine reduced increased levels of oxidative stress. In healthy men exposed to intensive exercise, alpha-lipoic acid provided antioxidant effects systemically (decreased peroxidation). L-acetyl carnitine improved neuroimaging correlates of cerebral blood flow in 30 subjects with dementia. These nutritional supplements have been safe and well-tolerated, and they have been tested in age groups including children, up to the elderly. Alpha-lipoic acid had been successfully administered over an extended period in an open-label trial in Alzheimer's disease. Importantly, it appeared that the effects of alpha-lipoic acid and L-acetyl carnitine when administered together were significantly augmented (100-1000 times), as opposed to when administered separately. This therefore provided a strong rationale to test the two in combination.
In addition to monitoring clinical features, we had also chosen to test physiologic effects of alpha-lipoic acid/L-acetyl carnitine in our PSP subjects using two biomarkers that provide measures of mitochondrial function and oxidative stress. This was particularly important, since both supplements may act by multiple mechanisms. 1H MRSI is a technique that provides insight into the metabolism of several endogenous brain compounds, most notably N-acetyl-L-aspartate (NAA), choline-containing compounds (Cho), and creatine and phosphocreatine (Cr). A number of studies of mitochondrial function had firmly established the utility of 1H MRSI in probing potential mitochondrial energy metabolism dysfunction. 31P MRSI provided complementary information to probe in vivo mitochondrial energy metabolism and tissue energetics. In addition, we proposed using markers of oxidative damage (including 8-hydroxydeoxyguanosine) as well as metabolomic analysis to test a composite panel of quantitative measures in plasma. We used an established metabolomic platform that has proven to identify specific combinations of metabolites differing between neurodegenerative disease states (including Parkinson's disease, Huntington's disease) and healthy controls. Our overall aim was to generate an "oxidative biomarker" and "metabolomic read-out" of the peripheral biochemical effects of alpha-lipoic acid/L-acetyl carnitine in PSP.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
New York
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New York, New York, United States, 10021
- Weill Cornell Medical College
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of probable PSP by NINDS/PSP workshop criteria (see patient folder)
- Age 40-75 years
- Able to undergo MRI
- Absence of significant medical, psychiatric, and other neurological disease
- Stable intake of supplements and medication
Exclusion Criteria:
- Failure to meet probable PSP diagnosis by NINDS/PSP workshop criteria
- unable to comply with informed consent process
- unable to undergo MRI
- presence of significant medical, psychiatric (incl MDD) or other neurological (incl epilepsy, brain tumor, stroke) disease
- possibility of pregnancy (negative test required in women of childbearing age)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Juvenon
|
alpha-lipoic acid and L-acetyl carnitine capsules, 600mg/1.5g
daily for 6 months
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events
Time Frame: at 25 weeks
|
Incidence and severity of adverse events
|
at 25 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cerebral Oxidative Stress Markers
Time Frame: at baseline and at week 5
|
changes of cerebral lactate and glutathione levels as determined by magnetic resonance spectroscopy
|
at baseline and at week 5
|
Collaborators and Investigators
Investigators
- Principal Investigator: Claire Henchcliffe, MD DPhil, Weill Medical College of Cornell University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Eye Diseases
- Neurologic Manifestations
- Basal Ganglia Diseases
- Movement Disorders
- Neurodegenerative Diseases
- Tauopathies
- Cranial Nerve Diseases
- Ocular Motility Disorders
- Ophthalmoplegia
- Paralysis
- Supranuclear Palsy, Progressive
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Protective Agents
- Micronutrients
- Vitamins
- Antioxidants
- Vitamin B Complex
- Nootropic Agents
- Acetylcarnitine
- Thioctic Acid
Other Study ID Numbers
- IRB1006011088
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Progressive Supranuclear Palsy
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Novartis PharmaceuticalsActive, not recruitingProgressive Supranuclear Palsy (PSP)Germany, United Kingdom, Canada, United States
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AbbVieTerminatedProgressive Supranuclear Palsy (PSP)United States, Australia, Canada, Italy, Japan
-
AbbVieCompletedProgressive Supranuclear Palsy (PSP)United States
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Assistance Publique Hopitaux De MarseilleCompletedProgressive Supranuclear Palsy (PSP)France
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Oregon Health and Science UniversityEunice Kennedy Shriver National Institute of Child Health and Human Development... and other collaboratorsRecruitingSupranuclear Palsy, Progressive | Palsy SupranuclearUnited States
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University of California, San FranciscoNational Institutes of Health (NIH); National Institute on Aging (NIA)Active, not recruitingProgressive Supranuclear Palsy (PSP) | Corticobasal Degeneration (CBD) | Nonfluent Variant Primary Progressive Aphasia (nfvPPA) | Corticobasal Syndrome (CBS) | Cortical-basal Ganglionic Degeneration (CBGD) | Oligosymptomatic/Variant Progressive Supranuclear Palsy (o/vPSP)United States, Canada
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University of California, San FranciscoTau Consortium; CBD SolutionsCompletedProgressive Supranuclear Palsy (PSP) | Corticobasal Degeneration (CBD) | Corticobasal Syndrome (CBS) | Primary Four Repeat Tauopathies (4RT)United States
-
UCB Biopharma SRLCompletedProgressive Supranuclear PalsyBelgium, Germany, Spain, United Kingdom
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Centre Hospitalier Universitaire de Pointe-a-PitreGroupe Hospitalier Pitie-Salpetriere; University Hospital Center of MartiniqueCompletedProgressive Supranuclear Palsy
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University of LouisvilleCompletedProgressive Supranuclear PalsyUnited States
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