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

NCT ID: NCT02046434

Last Updated: 2022-04-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2019-09-30

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.

Conditions

Parkinson's Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Parkinson's Diesase

Participant will take Glycerol Phenylbutyrate, participant has Parkinson's Disease

Group Type: EXPERIMENTAL

Glycerol Phenylbutyrate

Intervention Type: DRUG

Control

Participant does not have Parkinson's Disease, Participant will be taking glycerol phenylbutyrate

Group Type: EXPERIMENTAL

Glycerol Phenylbutyrate

Intervention Type: DRUG

Interventions

Glycerol Phenylbutyrate

Intervention Type: DRUG

Other Intervention Names

Ravicti

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.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Curt R Freed, MD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

University of Colorado Denver Anschutz Medical Center

Aurora, Colorado, United States

Countries

United States

References

Wen ZQ, Lin J, Xie WQ, Shan YH, Zhen GH, Li YS. Insights into the underlying pathogenesis and therapeutic potential of endoplasmic reticulum stress in degenerative musculoskeletal diseases. Mil Med Res. 2023 Nov 9;10(1):54. doi: 10.1186/s40779-023-00485-5.

Reference Type: DERIVED

PMID: 37941072 (View on PubMed)

Other Identifiers

13-2808

Identifier Type: -

Identifier Source: org_study_id