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
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.
Study Phase
Phase 1/Phase 2
Study Type
Interventional
Primary Outcome
Adverse Events
Secondary Outcome
Cerebral Oxidative Stress Markers
Condition
Progressive Supranuclear Palsy
Intervention
alpha-lipoic acid and L-acetyl carnitine
Study Arms / Comparison Groups
Juvenon
Description:
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
11
Start Date
September 14, 2010
Completion Date
April 7, 2015
Primary Completion Date
September 24, 2013
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)
Gender
All
Ages
40 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Claire Henchcliffe, MD DPhil, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01537549
Organization ID
IRB1006011088
Responsible Party
Sponsor
Study Sponsor
Weill Medical College of Cornell University
Study Sponsor
Claire Henchcliffe, MD DPhil, Principal Investigator, Weill Medical College of Cornell University
Verification Date
April 2017