Phenylbutyrate Response as a Biomarker for Alpha-synuclein Clearance From the Brain

• ClinicalTrials.gov Identifier: NCT02046434
• Recruitment Status: Completed
• First Posted: January 27, 2014
• Last Update Posted: April 25, 2022
• Sponsor: University of Colorado, Denver
• Information provided by (Responsible Party): University of Colorado, Denver

Tracking Information

• First Submitted Date: January 23, 2014
• First Posted Date: January 27, 2014
• Last Update Posted Date: April 25, 2022
• Actual Study Start Date: January 2014
• Actual Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 23, 2014): Levels of alpha-synuclein in blood plasma [ Time Frame: 1 month ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phenylbutyrate Response as a Biomarker for Alpha-synuclein Clearance From the Brain
• Official Title: Phenylbutyrate Response As a Biomarker for Alpha-Synuclein Clearance From Brain
• Brief Summary: This is a Phase I clinical trial of the FDA approved drug Glycerol Phenylbutyrate to see if phenylbutyrate can increase the removal of alpha-synuclein from the brain into the bloodstream. Alpha-synuclein forms abnormal protein deposits in dopamine neurons and is believed to cause the death of brain cells, leading to Parkinson's Disease.
• Detailed Description: This is a Phase I clinical trial of phenylbutyrate in 20 Parkinson patients and 20 age- and sex-matched normal control subjects to see if phenylbutyrate can increase the removal of alpha-synuclein from the brain into the bloodstream. All subjects will receive 20 grams/day of phenylbutyrate in the liquid form phenylbutyrate-triglyceride taken as one teaspoonful three times per day with meals. Blood will be drawn on two days prior to starting phenylbutyrate to measure alpha-synuclein concentrations. Phenylbutyrate-triglyceride will then be started and the change in plasma alpha-synuclein will be measured on day 1, 7, 14, and 21 days while taking phenylbutyrate. After 21 days, the drug will be stopped and a final blood sample will be measured at 28 days to see if plasma alpha-synuclein has fallen to its pre-phenylbutyrate level. No effects on Parkinson symptoms are expected during this short trial. Please note that although taking any type of Parkinson's drugs for symptomatic treatment disqualifies you, if you and your neurologist are willing and able to have you off Parkinson medication for six weeks before and during the trial, you may be eligible to participate.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Parkinson's Disease

Intervention

Drug: Glycerol Phenylbutyrate

Other Name: Ravicti

Study Arms

• Experimental: Parkinson's Diesase
  Participant will take Glycerol Phenylbutyrate, participant has Parkinson's Disease
  Intervention: Drug: Glycerol Phenylbutyrate
• Experimental: Control
  Participant does not have Parkinson's Disease, Participant will be taking glycerol phenylbutyrate
  Intervention: Drug: Glycerol Phenylbutyrate

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 15, 2022): 38
• Original Estimated Enrollment (submitted: January 23, 2014): 40
• Actual Study Completion Date: September 2019
• Actual Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Idiopathic Parkinson's disease with mild symptoms;

• May be on treatment with dopamine agonists provided that the treating neurologist agrees:

  1. that the drugs can be stopped for at least three weeks prior to participating in the phenylbutyrate study, and
  2. for the 4-week duration of the study.
• Age and sex matched normal control subjects from spouses and the general population;
• In good general health;
• Controlled hypertension, or
• Controlled hypercholesterolemia with medication.

Exclusion Criteria:

• Pregnant women;

• Current treatment with:

  1. L-3,4-dihydroxyphenylalanine (L-DOPA);
  2. monoamine oxidase (MAO) inhibitors,
  3. catechol-O-methyl transferase (COMT) inhibitors;
  4. histone deacetylase (HDAC) inhibitors;
  5. prednisone or other corticosteroids, or
  6. probenecid.

• Severe cardiopulmonary disease such as:

  1. congestive heart failure, or
  2. emphysema requiring supplemental oxygen;
• Renal disease with serum creatinine greater than 2.5;

• History of:

  1. depression in the prior year;
  2. epilepsy;
  3. stroke;
  4. prior brain surgery;
  5. dementia, or
  6. psychosis.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02046434
• Other Study ID Numbers: 13-2808
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Colorado, Denver
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Colorado, Denver
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Curt R Freed, MD; University of Colorado, Denver

• PRS Account: University of Colorado, Denver
• Verification Date: April 2022