Using Heavy Water to Study Cell Dynamics in Parkinson's Disease

Cellular and Molecular Kinetics of Cerebrospinal Fluid (CSF) Using Heavy Water Labeling Method: A Study of Healthy Controls, CNS HIV Infection, Parkinson's Disease and Other Neurodegenerative Diseases

This pilot study will assess the feasibility of using heavy water as a safe 'tracer' for biomarker studies of diseases of the brain and spinal cord, that, together, are also called the central nervous system (CNS). Heavy water, also called deuterated water or D20, is the same as normal drinking water except the hydrogen atoms have been replaced by deuterium, a naturally occurring isotope of hydrogen. In particular, this study will use heavy water to define: 1) The rate of immune cell proliferation (growth) in the cerebrospinal fluid (CSF) compared to blood. This study will be examining a particular type of immune cell called T lymphocytes. 2) This study will also examine selected molecules generated by nerve cells of the CNS to understand their rate of secretion and turnover in healthy control participants, HIV-1-infected participants and participants with a non-HIV-related neurodegenerative disease such as Parkinson's disease (PD).

This study will involve the administration of heavy water orally for either seven days, 12 days or six weeks. Measurements will be taken by lumbar puncture (LP, also known as a spinal tap). Blood (approximately five tablespoons per visit) will also be obtained at each of the lumbar puncture appointments.

If this method can be used to establish the rates of immune cell turnover and the production rates of neuronal molecules using cerebrospinal fluid, it will provide unique data that is important to understand chronic neurodegenerative conditions, like PD, and to measure responses to targeted therapies.

Hypothesis:

1. D2O, administered orally, can be used to measure the proliferation rates of CSF T cells (and, eventually, of their major phenotypic subsets).
2. D2O can be used to assess the turnover and production rates of CNS constituents that are normally or pathologically shed or secreted into the CSF, including (eventually): cargo molecules transported specifically in neurons in the CNS, such as chromogranin-A and -B, neuregulin-1 (specifically the extracellular secreted ectodomain of neuronal differentiation factor (NDF) isoform type α1, α2, β1, and the acetylcholine receptor inducing activity isoform (ARIA), secreted amyloid precursor protein (sAPP), alpha-synuclein; and APP metabolites amyloid beta (Aβ) 41 and 42.

Study Overview

• Status: Unknown
• Conditions: HIV Infections; Parkinson's Disease

• Study Type: Observational
• Enrollment (Anticipated): 45

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • San Francisco General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy controls, HIV positive (on or off ARVs), patients diagnosed with Parkinson's Disease.

All subjects must be 18 years of age or older.

Description

Inclusion Criteria:

• 18 years of age or older
• healthy controls with no significant medical conditions
• diagnosed HIV positive patients on or off ARVs
• diagnosed Parkinson's Disease patients
• capacity to provide informed consent

Exclusion Criteria:

• none

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Controls; Healthy men and women, 18 years of age or older, who have no history of significant medical conditions.
HIV positive; Men and women, 18 years of age or older, who have been diagnosed with HIV infection. Patients may be on or off of ARVs.
Parkinson's Disease; Men and women, 18 years of age or older, who have been diagnosed with Parkinson's Disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
CSF Biomarkers	40 days

Collaborators and Investigators

• Sponsor: Salena Killion
• Collaborators: Michael J. Fox Foundation for Parkinson's Research
• Investigators: Principal Investigator: Richard Price, MD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Anticipated): February 1, 2016
• Study Completion (Anticipated): February 1, 2016

Study Registration Dates

• First Submitted: October 2, 2009
• First Submitted That Met QC Criteria: October 5, 2009
• First Posted (Estimate): October 6, 2009

Study Record Updates

• Last Update Posted (Estimate): March 31, 2015
• Last Update Submitted That Met QC Criteria: March 30, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: HIV; HIV positive; brain diseases; spinal fluid
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Slow Virus Diseases; HIV Infections; Parkinson Disease; Infections; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: 6076

Drug and device information, study documents

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