Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment

NCT02967250 | Completed Phase 1 FDA Drug

• 1 other identifier: NEUR-2016-18222
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of this study is to understand the bioenergetic impairments that underlie Parkinson's disease (PD) and evaluating treatments that may improve abnormal mitochondrial function that is present in PD. The hypothesis is that repeated oral dosing of UDCA will result in increased brain ATP levels in individuals with Parkinson's disease (PD). The specific aims are 1.) to measure plasma UDCA levels in individuals with PD at baseline and after four weeks of repeated high doses of oral UDCA (50mg/kg/day) and 2.) to measure cortical bioenergetic profile and ATPase activity (as ascertained through MRS) in those with PD at baseline and at four weeks after repeated high doses of oral UDCA (50mg/kg/day) simultaneously. Secondary aims are to characterize oral UDCA pharmacokinetics and develop a pharmacokinetic/pharmacodynamic model to characterize the relationship between peripheral measurements of UDCA (and associated conjugates) and peripheral measures and/or central (brain) bioenergetic measurements.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• Change in ATP concentration

  measurement of ATP concentrations in brain using 7T MRS

  prior to intervention and at 6 weeks of intervention

Secondary Outcomes (1)

• UDCA pharmacokinetics

  at 6 weeks of intervention

Study Arms (1)

Ursodeoxycholic acid treatment

EXPERIMENTAL

Each subject will receive UDCA intervention for six weeks.

Drug: ursodeoxycholic acid

Interventions

ursodeoxycholic acid DRUG

Subjects will be provided \~50mg/kg/day (based on the use of 250 and 500mg capsules) of UDCA to be divided into 3 equal daily doses and titrated up over \~2 weeks to a stable dose for 4 weeks.

Also known as: Ursodiol

Ursodeoxycholic acid treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants must be 18 years or older.
• All enrollees must understand and cooperate with requirements of the study and be able to provide written informed consent
• Individuals with medically stable mild to moderate Parkinson's disease or healthy controls (as determined by enrolling investigator)
• All participants must not have taken UDCA for 4 weeks prior to the study.
• Absence of dementia in all subjects, as determined by pre-scanning cognitive assessment.

You may not qualify if:

• Inability to undergo MRI scanning without sedation and other MRI counterindications, such as metal in the body.
• Medically unstable conditions
• Pregnant or lactating or those women of child-bearing age that are not using acceptable forms of contraception
• Unable to adhere to study protocol as determined by the PI

Sponsors & Collaborators

• University of Minnesota: lead

Study Sites (1)

Center for Magnetic Resonance Research

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Ursodeoxycholic Acid

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes

Study Officials

• Lisa Coles, PhD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Paul Tuite, MD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: November 18, 2016
• Study Start: April 1, 2020
• Primary Completion: February 28, 2022
• Study Completion: February 28, 2022
• Last Updated: March 22, 2022

Record last verified: 2022-03

Locations

US (1)