Clinical trial NCT02046434: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson's Disease
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
First posted: 2014-01-27
Enrollment: 38
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Levels of alpha-synuclein in blood plasma
timeFrame: 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Denver Anschutz Medical Center
state: Colorado
Study officials:
affiliation: University of Colorado, Denver
name: Curt R Freed, MD
role: PRINCIPAL_INVESTIGATOR
References: