Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy
Primary Purpose
Progressive Supranuclear Palsy
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
alpha-lipoic acid and L-acetyl carnitine
Sponsored by
About this trial
This is an interventional treatment trial for Progressive Supranuclear Palsy focused on measuring Progressive supranuclear palsy, alpha-lipoic acid, L-acetyl carnitine, antioxidant, magnetic resonance spectroscopy, neurodegeneration, glutathione
Eligibility Criteria
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)
Sites / Locations
- Weill Cornell Medical College
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Juvenon
Arm Description
Outcomes
Primary Outcome Measures
Adverse Events
Incidence and severity of adverse events
Secondary Outcome Measures
Cerebral Oxidative Stress Markers
changes of cerebral lactate and glutathione levels as determined by magnetic resonance spectroscopy
Full Information
NCT ID
NCT01537549
First Posted
January 9, 2012
Last Updated
April 24, 2017
Sponsor
Weill Medical College of Cornell University
1. Study Identification
Unique Protocol Identification Number
NCT01537549
Brief Title
Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy
Official Title
An Open-label Trial of Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy (PSP): Effect Upon Oxidative Damage and Mitochondrial Biomarkers
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
September 14, 2010 (Actual)
Primary Completion Date
September 24, 2013 (Actual)
Study Completion Date
April 7, 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Supranuclear Palsy
Keywords
Progressive supranuclear palsy, alpha-lipoic acid, L-acetyl carnitine, antioxidant, magnetic resonance spectroscopy, neurodegeneration, glutathione
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Juvenon
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
alpha-lipoic acid and L-acetyl carnitine
Other Intervention Name(s)
Juvenon
Intervention Description
alpha-lipoic acid and L-acetyl carnitine capsules, 600mg/1.5g daily for 6 months
Primary Outcome Measure Information:
Title
Adverse Events
Description
Incidence and severity of adverse events
Time Frame
at 25 weeks
Secondary Outcome Measure Information:
Title
Cerebral Oxidative Stress Markers
Description
changes of cerebral lactate and glutathione levels as determined by magnetic resonance spectroscopy
Time Frame
at baseline and at week 5
10. Eligibility
Sex
All
Minimum Age & Unit of Time
40 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claire Henchcliffe, MD DPhil
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy
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