P-glycoprotein Function in Brain Diseases

NCT00677885 | Completed

• 2 other identifiers: 08012408-M-0124
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will measure the function of a protein called P-glycoprotein (P-gp), which is found at the blood-brain barrier, a membrane that normally prevents toxic material from entering the brain. Impaired P-gp function may allow toxins to enter the brain and cause some people to develop certain brain diseases. Healthy subjects and people with Alzheimer s disease, Parkinson s disease or frontotemporal dementia who are 35 years of age or older and in overall good health may be eligible for this study. Participants undergo the following procedures during three outpatient visits to the NIH Clinical Center:

• Medical history, psychological evaluation, physical examination and blood and urine tests, including tests for illegal and addictive drugs.
• PET scan: This test uses small amounts of a radioactive chemical called a tracer that labels active areas of the brain so the activity can be seen with a special camera. Before starting the scan, a catheter (plastic tube) is placed in a vein in the arm to inject the tracer. The subject lies on the scanner bed, with a special mask fitted to the head and attached to the bed to help keep the head still during the scan so the images obtained are clear. A brief initial scan is done to calibrate the scanner. Then, a radioactive tracer called \[(15)O\]H(2)O is injected into the catheter and the PET camera takes pictures of blood flow to the brain for about 60 seconds. Next, another tracer, \[(11)C\]dLop, is injected into the catheter and pictures are taken for about 2 hours to determine how much of this tracer is allowed to enter the brain.
• Magnetic resonance imaging (MRI): This procedure is done within 1 year (before or after) the PET scan. MRI uses a magnetic field and radio waves to produce images of the brain. For this procedure, the patient lies on a table that can slide in and out of the scanner (a tube-like device), wearing earplugs to muffle loud knocking and thumping sounds that occur during the scan.

Conditions

Alzheimer Disease; Parkinson Disease; Frontotemporal Lobar Degeneration

Keywords

Alzheimer Disease; Parkinson's Disease; Frontotemporal Dementia; PET Imaging; AD; Parkinson Disease; PD

Outcome Measures

Primary Outcomes (1)

• P-gp function in AD, PD, and FTD patients and in healthy volunteers. P-gp function will be determined by calculating the brain uptake of [11C]dLop

Secondary Outcomes (1)

• Comparing P-gp function with the severity of disease

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with the diagnosis of probable Alzheimer disease, Parkinson disease, or frontotemporal dementia. All patients must either meet capacity criteria to consent to research, or be able to assign a surrogate decision-maker who is able to consent to research on the subject s behalf.
• Healthy volunteers.

You may not qualify if:

• Current psychiatric disease, substance abuse or severe systemic disease based on history and physical exam.
• Laboratory tests with clinically significant abnormalities.
• Subjects on blood-thinning medications, having coagulation disorders, or clinically significant abnormal blood clotting test (PT/PTT).
• Prior participation in other research protocols or clinical care in the last year such that radiation exposure, including that from this protocol, would exceed the guidelines set by the Radiation Safety Committee (RSC).
• Pregnancy or breast feeding.
• Positive result on urine screen for illicit drugs.
• Subjects who cannot lie on their back for extended periods of time.
• History of neurological disease other than Alzheimer disease, Parkinson disease, or frontotemporal dementia.
• Subjects who have a cardiac pacemaker or metal in their body.
• Subjects taking cyclosporine A.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Hochman JH, Pudvah N, Qiu J, Yamazaki M, Tang C, Lin JH, Prueksaritanont T. Interactions of human P-glycoprotein with simvastatin, simvastatin acid, and atorvastatin. Pharm Res. 2004 Sep;21(9):1686-91. doi: 10.1023/b:pham.0000041466.84653.8c.

  PMID: 15497697 BACKGROUND

• Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW. Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. doi: 10.1124/jpet.102.039255.

  PMID: 12438524 BACKGROUND

• Schwab D, Fischer H, Tabatabaei A, Poli S, Huwyler J. Comparison of in vitro P-glycoprotein screening assays: recommendations for their use in drug discovery. J Med Chem. 2003 Apr 24;46(9):1716-25. doi: 10.1021/jm021012t.

  PMID: 12699389 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Parkinson Disease; Frontotemporal Lobar Degeneration; Frontotemporal Dementia

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• William C Kreisl, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH

Study Record Dates

• First Submitted: May 13, 2008
• First Posted: May 15, 2008
• Study Start: May 9, 2008
• Study Completion: August 25, 2014
• Last Updated: November 22, 2019

Record last verified: 2014-08-25

Locations

US (1)