Clinical trial NCT03716258: Characterizing Biomarkers of Early Parkinson's Disease Progression (TREG)
Official title: Characterizing Biomarkers of Early Parkinson's Disease Progression
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Parkinson Disease
Movement Disorders
Keywords: Parkinson Disease
Biomarkers
Inflammation
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
Collaborators: name: Portland VA Medical Center
First posted: 2018-10-23
Enrollment: 16
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Early, untreated Parkinson's disease

Brief summary: The purpose of this study is to look at a blood marker of inflammation in early untreated Parkinson's disease.

Detailed description: Objectives:

Parkinson's disease is the second most common neurodegenerative condition worldwide, and while both motor and non-motor symptoms can be improved with symptomatic therapies, there are currently no drugs that slow or halt progression of the disease. All previous trials of neuroprotective therapies have failed, in large part due to the lack of objective, sensitive biomarkers of Parkinson's disease progression.

Plan:

The proposed study aims to characterize the rate of change in a peripheral blood marker of inflammation (Treg percentage) and three quantitative motor measures (finger tapping, 9-hole peg test and peak turn velocity) in a cohort of 25 untreated PD patients with motor testing and blood sampling performed at baseline and at 6 months

Methods:

Participants will have three visits to the Portland VA over a 12 month period. Assessments will be made regarding their Parkinson's disease progression (motor ability and gait and balance). At each visit, a VA phlebotomist will draw whole blood. The VA lab will analyze whole blood for metabolic CBC with differential. The research team will hand carry blood samples from the VA phlebotomist to Dr. Quinn's VA lab in BLDG 103 - E143. A plasma sample will be added to the Neurologic Disorders Repository (MIRB # 3129). Peripheral blood mononuclear cells (PBMC) will be isolated from buffy coats using Ficoll-Paque. The PBMC will be frozen and batch analyzed for T lymphocytes using flow cytometry at OHSU.

Eligibility criteria: Inclusion Criteria:

* Men and women between the ages of 40 and 80 years
* Diagnosis of idiopathic Parkinson's disease based on the UK PD Brain Bank criteria35
* PD diagnosis within 5 years (≤ 5 years)
* Hoehn and Yahr severity stage less than or equal to 3 (Mild to moderate bilateral disease; some postural instability; physically independent).36
* Remain untreated with levodopa or a dopamine agonist for the duration of the study (up to 7 months, can have treatment with MAO-B inhibitors rasagiline or selegiline)
* Able to understand and give informed consent for the study
* Able to stand and walk unassisted

Exclusion Criteria:

* Current use of dopamine-blocking therapy or significant history of dopamine-blocking therapy (\> 1 yr of daily use of the following: typical and atypical antipsychotics except for quetiapine and clozapine, metoclopramide, prochlorperazine, tetrabenazine, reserpine)
* Autoimmune disease or current anti-inflammatory or immunomodulatory therapy (aspirin, Tylenol, ibuprofen, naproxen OK)
* Other condition already causing gait dysfunction or likely to cause significant change in motor/gait function over 6 month period (i.e. knee or hip replacement within the past 6 months or surgery planned during the study, peripheral neuropathy causing impaired proprioception at big toes)
* History of treatment with carbidopa/levodopa, dopamine agonist, or amantadine (can have history of treatment with MAO-B inhibitors rasagiline or selegiline)
* Patient anticipates that they will require symptomatic treatment for PD within the next 6 months

Primary outcomes:
measure: Peripheral Blood Treg Percentage (1 year)
timeFrame: Enrollment and 12 months
Secondary outcomes:
measure: Peripheral Blood Treg Percentage (6 months)
timeFrame: Enrollment and 6 months
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Portland
country: United States
facility: VA Portland Health Care System
state: Oregon
Study officials:
affiliation: Oregon Health and Science University
name: Joseph F Quinn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Monahan AJ, Warren M, Carvey PM. Neuroinflammation and peripheral immune infiltration in Parkinson's disease: an autoimmune hypothesis. Cell Transplant. 2008;17(4):363-72.
citation: Saunders JA, Estes KA, Kosloski LM, Allen HE, Dempsey KM, Torres-Russotto DR, Meza JL, Santamaria PM, Bertoni JM, Murman DL, Ali HH, Standaert DG, Mosley RL, Gendelman HE. CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson's disease. J Neuroimmune Pharmacol. 2012 Dec;7(4):927-38. doi: 10.1007/s11481-012-9402-z. Epub 2012 Oct 11.
citation: Mancini M, Carlson-Kuhta P, Zampieri C, Nutt JG, Chiari L, Horak FB. Postural sway as a marker of progression in Parkinson's disease: a pilot longitudinal study. Gait Posture. 2012 Jul;36(3):471-6. doi: 10.1016/j.gaitpost.2012.04.010. Epub 2012 Jun 29.
citation: Haaxma CA, Bloem BR, Borm GF, Horstink MW. Comparison of a timed motor test battery to the Unified Parkinson's Disease Rating Scale-III in Parkinson's disease. Mov Disord. 2008 Sep 15;23(12):1707-17. doi: 10.1002/mds.22197.