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Trial record 2 of 3 for:    01-M-0254

Evaluation of a Novel PET Radioligand to Image Cyclooxygenase-1 (COX-1)

This study is currently recruiting participants.
Verified September 28, 2017 by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
Sponsor:
ClinicalTrials.gov Identifier:
NCT03324646
First Posted: October 30, 2017
Last Update Posted: November 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
  Purpose

Background:

A radioligand is a radioactive substance that is used to diagnose diseases. A new ligand is called [11C]PS13. This has a small amount of radioactivity that can be detected by a positron emission tomography (PET) scan. If this ligand works well in this study, researchers may be able to use it to better understand and diagnose brain disorders.

Objectives:

To evaluate if [11C]PS13 can measure its receptor, which is involved in inflammation. To see if researchers get the same results when scanning a person twice.

Eligibility:

Healthy people ages 18 and older who are in Protocol 01-M-0254.

Design:

This study requires three visits of 2 5 hours each.

Participants will have 2 PET scans with [11C]PS13.

A needle will guide a small plastic tube (catheter) into an arm vein. The needle will be removed, leaving only the catheter in the vein. The ligand will be injected through the catheter.

The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner.

Participants will wear a molded a plastic mask that fits the head.

Another catheter will be put into an artery at the wrist or elbow area.

Vital signs will be monitored during the PET scan. Participants will have a test during the PET scan to monitor heart function.

Participants will have blood and urine tests.

Participants will have 1 magnetic resonance imaging (MRI) scan. The MRI scanner is a metal cylinder surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder.


Condition
Adult

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Evaluation of a Novel PET Radioligand to Image Cyclooxygenase-1 (COX-1)

Further study details as provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):

Primary Outcome Measures:
  • The identifiability and time stability of distribution volume calculated with compartmental modeling. [ Time Frame: ongoing ]

Estimated Enrollment: 31
Actual Study Start Date: October 3, 2017
Estimated Study Completion Date: January 31, 2022
Estimated Primary Completion Date: January 31, 2022 (Final data collection date for primary outcome measure)
Groups/Cohorts
Healthy Volunteers
Healthy adult female and male volunteers age 18 or older

Detailed Description:

Objective

The cyclooxygenase (COX) system is implicated in the pathophysiology of brain diseases, including Alzheimer s disease and depression, and is a potential biomarker for neuroinflammation. COX is the rate-limiting enzyme in the synthesis of prostaglandins from arachidonic acid and exists as two primary isoforms COX-1 and COX-2. Our laboratory recently developed [(11)C]PS13, a novel PET ligand to selectively image COX-1, and initial PET scans in monkey demonstrated that [11C]PS13 is a promising ligand.

This study has two primary objectives. First, we will determine whether the uptake of [(11)C]PS13 in brain and periphery reflects the distribution of COX-1, as demonstrated by blocking with a COX-1 preferential drug (aspirin) and no effect with a COX-2 selective drug (celecoxib). Second, we will measure the test/retest reproducibility of brain uptake quantified by compartmental modeling and using arterial blood samples.

Study Population

Healthy adult female and male volunteers (age 18 or older) will have either whole body imaging (n = 16) or brain imaging (n = 15).

Design

Phase 1: We will begin with whole body scanning in a single human subject using up to 10 mCi. The aim of this first scan will be to detect a tracer that disproportionately accumulates in a single radiosensitive organ, such as the gonads. If we confirm that radioactivity is fairly widely distributed in the body, higher activities may be injected.

Phase 2: Fifteen healthy subjects will have three whole body imaging PET scans using 20 mCi of [11C]PS13. Scan 1 will serve as the baseline scan for comparison to enzyme occupancy studies and will provide dosimetry information. Scan 2 will be an enzyme occupancy study using the COX-2 selective antagonist celecoxib. Scan 3 will be an enzyme occupancy study using the COX-1 preferential antagonist aspirin.

Phase 3: We will perform 15 test retest kinetic brain imaging PET studies with arterial blood sampling using a 20 mCi dose of [(11)C]PS13.

Outcome Measures

For whole body imaging, organ uptake will be quantified as a Standardized Uptake Value (SUV), which normalizes for injected activity and body weight. Blockade by aspirin and celecoxib will be expressed as a percentage of the baseline scan in each subject and plotted relative to the plasma concentration of the drug at time of the PET scan. For dedicated brain imaging, uptake will be quantified as distribution volume (VT) calculated with compartmental modeling and serial concentrations of parent radioligand in arterial plasma.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 100 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Healthy adult female and male volunteers
Criteria
  • INCLUSION CRITERIA:
  • Age greater than or equal to 18.
  • Able to give written informed consent.
  • Medically and psychiatrically healthy.
  • Enrolled in 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers (PI: Dr. Carlos Zarate).

EXCLUSION CRITERIA All phases

  • Because non-steroidal anti-inflammatory drugs (NSAIDs) inhibit COX-1 and/or COX-2, subjects should not have taken NSAIDs for two weeks prior to the PET scan. In addition, aspirin must not have been taken in the prior month, as aspirin irreversibly inhibits COX.
  • Clinically significant laboratory abnormalities based on tests performed under screening protocol 01-M-0254
  • Any current Axis I diagnosis, based on interview and self-reporting performed under screening protocol 01-M-0254.
  • Positive HIV test.
  • History of medical or neurologic illness or injury with the potential to affect study data interpretation.
  • Recent exposure to radiation related to research (i.e. PET from other research) that, when combined with this study, would be above the allowable limits.
  • Inability to lie flat on camera bed for at least two hours.
  • Pregnancy or breastfeeding.
  • Current drug/alcohol abuse or dependence.
  • Current use of psychiatric medications.
  • NIMH employees and staff

EXCLUSION CRITERIA Phase 2:

  • Because aspirin and celecoxib require an acidic environment to be absorbed in the stomach, we will exclude those who have taken proton pump inhibitor (PPI) drugs, H-2 receptor antagonist drugs, and antacid drugs in the last two weeks.
  • additional contraindications to taking COX-1 or COX-2 inhibitors include:

    • history of hypersensitivity reaction to COX inhibitors history of aspirin- or NSAID-induced asthma;
    • history of upper or lower gastrointestinal bleeding, gastritis, peptic ulcer disease, or gastroesophageal reflux disease (GERD);
    • coagulation disorder;
    • thrombocytopenia;
    • G6PD deficiency;
    • history of gout;
    • history of hepatic or renal impairment;
    • history of cardiovascular disease or presence of cardiovascular risk factors such as hypertension.

EXCLUSION CRITERIA Phase 3:

  • Artery check for art line
  • Unable to have an MRI scan

NIH employees are eligible to participate. NIMH employee participation is guided by intramural institute policy.

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03324646


Contacts
Contact: Holly Giesen (301) 435-8982 giesenh@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
Principal Investigator: Robert B Innis, M.D. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT03324646     History of Changes
Other Study ID Numbers: 170179
17-M-0179
First Submitted: October 27, 2017
First Posted: October 30, 2017
Last Update Posted: November 6, 2017
Last Verified: September 28, 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
PET Imaging