Image Parkinson's Disease Progression Study

NCT02789020 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB201600537-NR01NS052318
• Study Type: interventional
• Target: 96
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Parkinson's Disease

Keywords

Rasagiline

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Changes in Parkinson's Disease Motor Symptoms and Bradykinesia

  Baseline and one-year

• Changes Between the Groups on fMRI

  Changes from baseline to 1 year

Study Arms (2)

Rasagiline

EXPERIMENTAL

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; Device: Magnetic Resonance Imaging; Device: functional Magnetic Resonance Imaging; Other: Physical Function Performance Test

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo; Device: Magnetic Resonance Imaging; Device: functional Magnetic Resonance Imaging; Other: Physical Function Performance Test

Interventions

Rasagiline DRUG

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.

Also known as: Azilect, MAO-B inhibitor

Rasagiline

Placebo OTHER

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.

Placebo

Magnetic Resonance Imaging DEVICE

This test will be performed at baseline and one year.

Also known as: MRI

Placebo; Rasagiline

functional Magnetic Resonance Imaging DEVICE

This test will be performed at baseline and one year.

Also known as: fMRI

Placebo; Rasagiline

Physical Function Performance Test OTHER

This test will be performed at baseline and one year.

Placebo; Rasagiline

Eligibility Criteria

• Age: 40 Years - 77 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Laboratory for Rehabilitation Neuroscience

Gainesville, Florida, 32611, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

rasagiline; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Results Point of Contact

• Title: David Vaillancourt
• Organization: University of Florida

vcourt@ufl.edu

3522941770

Study Officials

• David E Vaillancourt, PhD.

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2016
• First Posted: June 2, 2016
• Study Start: December 1, 2016
• Primary Completion: May 11, 2023
• Study Completion: May 11, 2023
• Last Updated: September 6, 2023
• Results First Posted: September 6, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)