USDOE Human Subjects Research Database, fiscal year 1995

Brookhaven National Laboratory

Project Identifier: BNL-89-220

Project Title:

Whole Body Distribution of 11-C-Labeled Cogentin in Humans

Principle Investigator: Dr. Steven L. Dewey

Project started in: 1989

Fiscal Year 1995 Funding for Research on Human Subjects:

Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.

Funding Sources:

DOE: Office of Health and Environmental Research (OHER)

Amount: $79,000 (Est.)

Non-DOE Federal: National Institute of Mental Health (NIMH)

Amount: $129,000 (Est.)
Comments:

MH 49936

Total Funding: $208,000

Information on Use of Human Subjects:

Project does not involve use of multiple protocols/subprojects.

IRB Review:
Type of Review: Full Board
Most Recent Approval: February 01, 1995

Number of Human Subjects in the Last Reporting Period for this Project: 13
(Reporting periods vary.)

Type of Human Subjects Involvement:

Ionizing Radiation and Radioactive Substances:

External use of ionizing radiation on human subjects.

• For clinical research.

Internal administration of radioactive substances to human subjects.

• For clinical research.

Chemical Substances:

Internal use of chemical substances (solid, liquid, or gas) in human subjects.

• For clinical research.

Collection of Bodily Materials:

Collection of personally identifiable bodily materials (blood or blood products, cells, tissue, organs, waste).

• Use of bodily materials collected from subjects specifically for this project.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

This project proposes to use positron emission tomography (PET) to investigate the capacity to alter neurochemical function in response to acute neuroleptic-induced receptor blockade in chronic schizophrenia. F-18-Fluorodeoxyglucose (18-FDG) will be used in a repeated measure designed to examine regional changes in glucose metabolism following administration of a single pharmacological challenge dose of the neuroleptic drug haloperidol. This dose is sufficient to induce receptor blockage. Over a period of three years, approximately 24 subjects will be studied twice with 18-FDG. In the second part of these studies, PET and the muscarinic cholinergic ligand 11-C-benztropine (cogentin), intravenously administered, will be used to measure regional changes in muscarinic activity following intravenous administration of the haloperidol challenge on the separate, but functionally related muscarinic cholinergic system. These measures may provide a neurochemical basis for interpreting treatment response, for clinical sub-typing and for developing new treatment strategies. The subjects have a short-lived positron emitter tracer administered and are subsequently scanned with PET. A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at doses as low as those delivered in this procedure has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Several uncomfortable reactions may occur following the administration of haloperidol: sedation, listlessness, decreased motivation, decreased blood pressure, painful muscular contractions, allergic drug reactions, dry mouth or blurred vision. Muscular reactions can and will be relieved with benzotropine. Arterial catheterization has the following rare, but possible complications: pain during placement of the catheter, a risk of bleeding at the skin puncture site, the possibility of local infection and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues.