Alpha-lipoic Acid/L-acetyl Carnitine for Progressive Supranuclear Palsy

April 24, 2017 updated by: Weill Medical College of Cornell University

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
11

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Weill Cornell Medical College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Juvenon
Drug: alpha-lipoic acid and L-acetyl carnitine
alpha-lipoic acid and L-acetyl carnitine capsules, 600mg/1.5g daily for 6 months
Other Names:
  • Juvenon

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Weill Medical College of Cornell University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Claire Henchcliffe, MD DPhil, Weill Medical College of Cornell University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 14, 2010

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 24, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 7, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 9, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 22, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 23, 2012

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 30, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 24, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

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