Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment
Primary Purpose
Parkinson Disease
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ursodeoxycholic acid
Sponsored by
About this trial
This is an interventional treatment trial for Parkinson Disease
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
Sites / Locations
- Center for Magnetic Resonance Research
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Ursodeoxycholic acid treatment
Arm Description
Each subject will receive UDCA intervention for six weeks.
Outcomes
Primary Outcome Measures
Change in ATP concentration
measurement of ATP concentrations in brain using 7T MRS
Secondary Outcome Measures
UDCA pharmacokinetics
measurement of UDCA concentration in plasma will be used to determine pharmacokinetics
Full Information
NCT ID
NCT02967250
First Posted
September 13, 2016
Last Updated
March 7, 2022
Sponsor
University of Minnesota
1. Study Identification
Unique Protocol Identification Number
NCT02967250
Brief Title
Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment
Official Title
7T Magnetic Resonance Spectroscopy Monitoring Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
April 1, 2020 (Actual)
Primary Completion Date
February 28, 2022 (Actual)
Study Completion Date
February 28, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
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:
Measure plasma UDCA levels in individuals with PD at baseline and after four weeks of repeated high doses of oral UDCA (50mg/kg/day).
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:
Characterize oral UDCA pharmacokinetics
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ursodeoxycholic acid treatment
Arm Type
Experimental
Arm Description
Each subject will receive UDCA intervention for six weeks.
Intervention Type
Drug
Intervention Name(s)
ursodeoxycholic acid
Other Intervention Name(s)
Ursodiol
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in ATP concentration
Description
measurement of ATP concentrations in brain using 7T MRS
Time Frame
prior to intervention and at 6 weeks of intervention
Secondary Outcome Measure Information:
Title
UDCA pharmacokinetics
Description
measurement of UDCA concentration in plasma will be used to determine pharmacokinetics
Time Frame
at 6 weeks of intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lisa Coles, PhD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Paul Tuite, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Magnetic Resonance Research
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment
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