Image Parkinson's Disease Progression Study

Parkinson's disease (PD) is a neurodegenerative brain disorder that impairs the ability to perform functions such as grooming, dressing, cooking, and other activities of daily living. PD affected between 4.1 and 4.6 million people worldwide in 2005, and it is projected that up to 9.3 million people will be affected by 2030. Although current pharmacological therapies provide beneficial effects on motor symptoms of the disease (tremor, rigidity, and bradykinesia), intolerable disability eventually develops in most patients. A disease-modifying therapy that slows disease progression is a major unmet medical need in PD. Numerous agents have neuroprotective effects in pre-clinical laboratory models, but none have been shown to have indisputable disease-modifying effects in clinical trials for patients with PD.

The purpose of this research study is to investigate how the brain and motor behavior changes in PD over time in response to rasagiline which is a monoamine oxidase-B(MAO-B) inhibitor. The drug rasagiline will be tested in this study as the MAO-B inhibitor. Rasagiline has been prescribed for many years to treat symptomatic Parkinson's disease. It is FDA approved for the treatment of Parkinson's disease but has not been shown to slow disease progression. The outcome and impact of this study will provide the first evaluation of MAO-B inhibitors at slowing the progression of the nigrostriatal pathway using advanced Magnetic Resonance Imaging (MRI) and functional Magnetic Resonance Imaging (fMRI) methods in PD.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Rasagiline; Device: Magnetic Resonance Imaging; Device: functional Magnetic Resonance Imaging; Other: Physical Function Performance Test; Other: Placebo

Detailed Description

Participants will receive baseline testing to confirm a diagnosis of Parkinsonism and to determine eligibility in the research study. Half of the participants in this study will be in a group that will receive the study drug (rasagiline), and half will be in a group that will receive a placebo. A placebo is a pill that is made to look like the study drug, but it does not contain any active ingredients. A computer algorithm will randomly decide group assignment (like the flip of a coin). The study drug will be provided at the end of the first visit. The participants will not know which study drug is received, placebo or rasagiline.

During the research study the following test may occur: (1) questionnaires about quality of life and depression; (2) tests to measure strength and motor function; (3) tests to measure cognition; (4) orientation session to learn a precision gripping task; (5) functional MRI scan of the brain; (6) structural MRI scan of the brain.

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32611
      • Laboratory for Rehabilitation Neuroscience

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 77 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 96 patients with clinically diagnosed PD. For the PD diagnosis, we will use the University of Kentucky PD brain bank diagnostic criteria implemented by a movement disorders trained neurologist. Only early stage PD within 5 years of diagnosis who have never taken rasagiline will be included. 5 years since diagnosis was chosen to focus on early stages of PD, where MAO-B inhibitors have shown the most promise. PD are eligible to participate if they are age 40-77, Hoehn and Yahr stage < or equal to 2 when on medication, and able and willing to sign informed consent to be randomized to the placebo or active drug arm.

Exclusion Criteria:

• As necessitated by the risks of Magnetic Resonance Imaging, patients who have any type of implanted electrical device (such as a cardiac pacemaker or a neurostimulator), or a certain type of metallic clip in their body (i.e., an aneurysm clip in the brain), are not eligible for participation in the MRI portion of the study.
• Individuals who are claustrophobic will also be excluded from participation.
• Women who are or might be pregnant and nursing mothers are not eligible. Pregnancy tests will be carried out for each female subject prior to the MRI scan.
• Individuals with psychiatric disorders or dementia will be excluded, along with other neurologic and orthopedic problems that impair hand movements and walking.
• Individuals who have a history metalworking involving cutting processes such as grinding, filing, shaving, and threading, will need radiological clearance to participate in this study. Specifically, individuals who report a history of metalworking will be referred to Radiology at Shands University of Florida(UF) for an orbitofrontal x-ray. In addition, individuals who have sustained an eye injury involving metal will also be referred to Radiology at Shands UF for an orbitofrontal x-ray. Shands at UF will provide a written report stating whether the individual is safe for imaging at 3 Tesla. All expenses related to this procedure will be covered by the PI.
• Patients with a prior stroke or brain tumor are excluded. Patients will be excluded if they are unwilling to comply with the study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rasagiline; This group will receive a 1 mg rasagiline tablet to be taken once daily for one year. In addition, the following test will be performed: a Magnetic Resonance Imaging (MRI), functional Magnetic Resonance Imaging (fMRI), the Montreal Cognitive Assessment, Stroop, Digit Span, Hopkins Verbal Learning Test, Brief Test of Attention, Beck Depression Index, Hamilton Anxiety and Depression Rating Scales, Physical Function Performance Test, and Epworth Sleepiness Scale.	Drug: Rasagiline; Rasagiline will be taken for one year at the dose of 1mg a day. and subjects will undergo functional and structural brain imaging to determine if rasagiline is slowing the progression of Parkinson's Disease in the brain.; Other Names: Azilect; MAO-B inhibitor; Device: Magnetic Resonance Imaging; This test will be performed at baseline and one year.; Other Names: MRI; Device: functional Magnetic Resonance Imaging; This test will be performed at baseline and one year.; Other Names: fMRI; Other: Physical Function Performance Test; This test will be performed at baseline and one year.
Placebo Comparator: Placebo; This group will receive a placebo tablet in the same forum as the rasagiline tablet to be taken once daily for one year. In addition, the following test will be performed: a Magnetic Resonance Imaging (MRI), functional Magnetic Resonance Imaging (fMRI), the Montreal Cognitive Assessment, Stroop, Digit Span, Hopkins Verbal Learning Test, Brief Test of Attention, Beck Depression Index, Hamilton Anxiety and Depression Rating Scales, Physical Function Performance Test, and Epworth Sleepiness Scale.	Device: Magnetic Resonance Imaging; This test will be performed at baseline and one year.; Other Names: MRI; Device: functional Magnetic Resonance Imaging; This test will be performed at baseline and one year.; Other Names: fMRI; Other: Physical Function Performance Test; This test will be performed at baseline and one year.; Other: Placebo; A placebo tablet will be taken for one year, once a day, and at the same dose of 1mg. subjects will undergo functional and structural brain imaging to be compared with the group taking the rasagiline intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Free-water Accumulation in the Substantia Nigra	12-month study in PD to watch the effect of an Monoamine Oxidase-B inhibitor on the progressive increase of free-water accumulation in the substantia nigra. Recently, free-water diffusion MRI analysis using a bi-tensor model was developed to explicitly estimate the contribution of freely diffusing water molecules within the voxel. This free-water measure is expected to increase with atrophy-based neurodegeneration. Since substantia nigra degeneration occurs mostly in the posterior region of the substantia nigra in PD (ie. ventrolateral tier), we tested the hypothesis that free-water would be elevated in the posterior substantia nigra of PD.	Baseline and one-year
Change in Blood Oxygen Level-dependent(BOLD) Signal in the Posterior Putamen, M1, and Supplementary Motor Area(SMA).	12-month study in PD to watch the effect of an MAO-B inhibitor on BOLD signal in the posterior putamen, M1, and SMA.	Baseline and one-year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Parkinson's Disease Motor Symptoms and Bradykinesia	Motor testing batteries such as the Purdue Pegboard Test will be administered to measure changes in the progression of the PD motor symptoms and bradykinesia.	Baseline and one-year
Changes Between the Groups on fMRI	Participants will use their hand to squeeze an MRI compatible grip force transducer in the MRI unit.	Changes from baseline to 1 year

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: David E Vaillancourt, PhD., University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Actual): May 11, 2023
• Study Completion (Actual): May 11, 2023

Study Registration Dates

• First Submitted: May 20, 2016
• First Submitted That Met QC Criteria: May 26, 2016
• First Posted (Estimated): June 2, 2016

Study Record Updates

• Last Update Posted (Estimated): September 6, 2023
• Last Update Submitted That Met QC Criteria: August 15, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Rasagiline
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease Attributes; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Disease Progression; Parkinson Disease; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Monoamine Oxidase Inhibitors; Rasagiline
• Other Study ID Numbers: IRB201600537-N; R01NS052318 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data will be available without any personal identifiers included.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No