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

Phenylbutyrate Response As a Biomarker for Alpha-Synuclein Clearance From Brain

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Glycerol Phenylbutyrate

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
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Anschutz Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Parkinson's Diesase; Participant will take Glycerol Phenylbutyrate, participant has Parkinson's Disease	Drug: Glycerol Phenylbutyrate; Other Names: Ravicti
Experimental: Control; Participant does not have Parkinson's Disease, Participant will be taking glycerol phenylbutyrate	Drug: Glycerol Phenylbutyrate; Other Names: Ravicti

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Levels of alpha-synuclein in blood plasma	1 month

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): September 1, 2019

Study Registration Dates

• First Submitted: January 23, 2014
• First Submitted That Met QC Criteria: January 23, 2014
• First Posted (Estimate): January 27, 2014

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 15, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Antineoplastic Agents; Protective Agents; Cryoprotective Agents; Glycerol; 4-phenylbutyric acid
• Other Study ID Numbers: 13-2808