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

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ClinicalTrials.gov Identifier: NCT02967250
Recruitment Status : Recruiting
First Posted : November 18, 2016
Last Update Posted : March 15, 2018
Sponsor:
Information provided by (Responsible Party):
University of Minnesota - Clinical and Translational Science Institute

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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: ursodeoxycholic acid Phase 1

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  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 7T Magnetic Resonance Spectroscopy Monitoring Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment
Actual Study Start Date : June 1, 2017
Estimated Primary Completion Date : March 1, 2019
Estimated Study Completion Date : March 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Ursodiol

Arm Intervention/treatment
Experimental: Ursodeoxycholic acid treatment
Each subject will receive UDCA intervention for six weeks.
Drug: ursodeoxycholic acid
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 Name: Ursodiol




Primary Outcome Measures :
  1. Change in ATP concentration [ Time Frame: prior to intervention and at 6 weeks of intervention ]
    measurement of ATP concentrations in brain using 7T MRS


Secondary Outcome Measures :
  1. UDCA pharmacokinetics [ Time Frame: at 6 weeks of intervention ]
    measurement of UDCA concentration in plasma will be used to determine pharmacokinetics



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02967250


Contacts
Contact: Lisa Coles, PhD 4109264788 durh0016@umn.edu
Contact: Paul Tuite, MD (612) 625-9662 tuite002@umn.edu

Locations
United States, Minnesota
Center for Magnetic Resonance Research Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Lisa Coles    410-926-4788    durh0016@umn.edu   
Principal Investigator: Lisa Coles, MS, PhD         
Sub-Investigator: Paul Tuite, MD         
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Investigators
Principal Investigator: Lisa Coles, PhD University of Minnesota - Clinical and Translational Science Institute
Principal Investigator: Paul Tuite, MD University of Minnesota - Clinical and Translational Science Institute

Responsible Party: University of Minnesota - Clinical and Translational Science Institute
ClinicalTrials.gov Identifier: NCT02967250     History of Changes
Other Study ID Numbers: 131477
First Posted: November 18, 2016    Key Record Dates
Last Update Posted: March 15, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents