- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02967250
Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment
7T Magnetic Resonance Spectroscopy Monitoring Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment
Study Overview
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Minnesota
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Minneapolis, Minnesota, United States, 55455
- Center for Magnetic Resonance Research
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
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.
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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:
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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
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measurement of ATP concentrations in brain using 7T MRS
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prior to intervention and at 6 weeks of intervention
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
UDCA pharmacokinetics
Time Frame: at 6 weeks of intervention
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measurement of UDCA concentration in plasma will be used to determine pharmacokinetics
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at 6 weeks of intervention
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Paul Tuite, MD, University of Minnesota
- Principal Investigator: Lisa Coles, PhD, University of Minnesota
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NEUR-2016-18222
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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