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

March 7, 2022 updated by: University of Minnesota

7T Magnetic Resonance Spectroscopy Monitoring Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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. High field - 7 tesla (T) - magnetic resonance spectroscopy (MRS) is able to non-invasively assess for changes in brain energetics and will be used to evaluate the effects that repeated oral doses of the mitochondrial enhancer ursodeoxycholic acid (UDCA) has on brain bioenergetics derived from MRS measurements. This study will combine results obtained using MRS brain scans along with peripheral measurements of bile acids (e.g., total UDCA). This research will require at least 2 visits: baseline evaluation and at approximately 6 weeks after subjects are on a stable oral dose for 4 weeks. Participants will provide their medical history during the first visit, and undergo a physical examination and rating scale each visit (duration: ~1 hour) as well as a brain MRI scan (1-1.5 hours). Blood will be obtained at both visits to monitor for adverse effects as well as to assess for changes in bile acids from orally administered UDCA. If additional funding is obtained we may have another visit added between the first and second assessments to obtain additional blood measurements and MRS data.

Since there is extensive animal and cell model data supporting the rationale for a therapeutic trial of UDCA in PD, and because MRS methods can non-invasively detect changes in brain chemistry we propose a study to evaluate the effects of a 4-6 weeks of high-dose oral UDCA on central (brain) and peripheral measures (through MRS and blood measurements, respectively) in individuals with PD and healthy controls. The hypothesis and specific aims are as follows:

Hypothesis: Repeated oral dosing of UDCA will result in increased brain ATP levels in individuals with Parkinson's disease (PD).

Specific Aims:

  1. Measure plasma UDCA levels in individuals with PD at baseline and after four weeks of repeated high doses of oral UDCA (50mg/kg/day).
  2. 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 with Aim 1.

Secondary Aims:

  1. Characterize oral UDCA pharmacokinetics
  2. 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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Center for Magnetic Resonance Research

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ursodeoxycholic acid treatment
Each subject will receive UDCA intervention for six weeks.
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.
Other Names:
  • Ursodiol

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in ATP concentration
Time Frame: prior to intervention and at 6 weeks of intervention
measurement of ATP concentrations in brain using 7T MRS
prior to intervention and at 6 weeks of intervention

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
UDCA pharmacokinetics
Time Frame: at 6 weeks of intervention
measurement of UDCA concentration in plasma will be used to determine pharmacokinetics
at 6 weeks of intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Paul Tuite, MD, University of Minnesota
  • Principal Investigator: Lisa Coles, PhD, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 1, 2020

Primary Completion (Actual)

February 28, 2022

Study Completion (Actual)

February 28, 2022

Study Registration Dates

First Submitted

September 13, 2016

First Submitted That Met QC Criteria

November 15, 2016

First Posted (Estimate)

November 18, 2016

Study Record Updates

Last Update Posted (Actual)

March 22, 2022

Last Update Submitted That Met QC Criteria

March 7, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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