Cholinergic Nicotinic Receptors and Cognition in PD

NCT ID: NCT02076295

Last Updated: 2017-04-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 48 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2016-12-30

Brief Summary

Mild cognitive impairment and dementia are frequent non-motor complications of moderate to advanced Parkinson's disease. Brain positron emission tomography (PET) study findings confirm post-mortem evidence that cholinergic loss is related to cognitive impairment in Parkinson's disease. However, current cholinergic augmentation therapy is not always effective and it should only target those Parkinson's disease patients who have evidence of cholinergic system impairment. The objective of this study is to study the association of a particular subtype of cholinergic receptors, so-called nicotinic acetylcholine receptors, with cognition in Parkinson's disease using a novel PET marker of cholinergic system integrity.

Detailed Description

Parkinson's disease patients will undergo nicotinic acetylcholine receptor PET imaging with the radioligand [18F]flubatine and MRI on one day and extensive neuropsychological testing on another day. The degree of nicotinic receptor expression obtained with PET imaging will be correlated with the neuropsychology test results.

Positive [18F]flubatine PET findings in this study would establish nicotinic receptors as an important contributor to cognitive dysfunction in Parkinson's disease and could kindle pharmaceutical interest in pursuing these agents for Parkinson's disease applications.

We expect that lower nicotinic receptor expression is associated with impaired cognitive functioning in Parkinson's disease. In a personalized medicine approach the PET radioligand [18F]flubatine could serve as an important marker to identify those patients who are expected to benefit most from nicotinic receptor drug treatment.

Conditions

Parkinson's Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Parkinson's disease subjects

No interventions assigned to this group

Normal control subjects

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• PD subjects (M/F, non-smoking, ≥ 50 years old, Hoehn & Yahr stages 1-4)
• Normal control subjects (N=15, M/F, non-smoking, ≥ 50 years old)

Exclusion Criteria

• Active smoking, use of other tobacco products, or use of nicotinic drugs such as nicotine patches or varenicline.
• Subjects with contra-indications to MR imaging, including pacemakers or claustrophobia.
• Evidence of large vessel stroke or mass lesion on MRI.
• Use of (anti-)cholinergic or neuroleptic drugs.
• Dementia or severe cognitive impairment confirmed by clinical and detailed neuropsychological assessment precluding safe study participation, performing study procedures, or unable to follow directions by study personnel.
• Evidence of atypical parkinsonism on neurological exam.
• Subjects limited by participation in research procedures involving ionizing radiation.
• Pregnancy (test within 48 hours of each PET session) or breastfeeding

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Michael J. Fox Foundation for Parkinson's Research

OTHER

Sponsor Role: collaborator

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Martijn Muller

Research Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Martijn T Muller, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan Health System

Ann Arbor, Michigan, United States

Countries

United States

Other Identifiers

HUM00083054

Identifier Type: -

Identifier Source: org_study_id