Evaluation of a Novel PET Radioligand to Image OGA

Background:

O-GlcNAcase (OGA) is a brain enzyme. It may play a role in brain disorders like Alzheimer s disease. Researchers want to see if a new drug can be used with positron emission tomography (PET) scans to show OGA better. Researchers want to learn more about how it acts in healthy people.

Objectives:

To test if the new drug [18F]OGA-1 can measure its receptor. To determine whether the same results occur when scanning a person twice.

Eligibility:

Healthy adults age 18 and older who are already enrolled in a separate protocol.

Design:

Some participants will have 1 whole-body PET scan during one 4-hour visit to the clinic. Some will have 2-3 brain scans (PET and MRI) over 2-3 days.

For the PET scan, a needle will guide a thin plastic tube (IV catheter) into an arm vein. A small amount of radioactive chemical will be injected through the catheter. The needle will be removed. Only the catheter will be left in the vein.

Another IV catheter may be placed to draw blood.

Blood pressure, heart rate, and breathing rate will be measured. Participants will have an electrocardiogram.

Participants will lie on a bed that slides in and out of the donut-shaped scanner.

The scan will last 2-3 hours.

For brain PET scan, participants will wear a plastic mask to keep their head still.

For magnetic resonance imaging (MRI) scan, participants will lie on a table. The table slides in and out of the MRI scanner. This is a metal cylinder in a strong magnetic field. Participants will be in the scanner up to 1 hour.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Objective:

Tau, a microtubule associated protein, regulates axonal structure and function within neurons of the brain. Neurofibrillary tangles contain hyper-phosphorylated, insoluble tau protein and are a hallmark of Alzheimer s disease (AD) and other tauopathies. Hyperphosphorylation of tau is required for its aggregation into tangles. One novel strategy to decrease the phosphorylation of tau is to increase the number of sugar molecules attached to tau, with the overly simple mechanism that the presence of the sugar molecules physically blocks phosphorylation. In this case, the sugar molecule is N-acetyl-Beta-D-glucosamine (GlcNAc), and increased glycosylation is achieved by inhibiting the enzyme (OGA) that removes these residues.

In collaboration with Eli Lilly, our laboratory recently developed (18F)OGA-1, a novel PET ligand to image the hydrolase OGA (O-GlcNAcase). Initial PET scans in monkey demonstrated that (18F)OGA-1 is a promising ligand.

This protocol is a first-in-human evaluation of (18F)OGA-1 and has four phases:

  1. Phase 1: whole body imaging of one (1) subject with a low injection activity of approximately 2 mCi to confirm that no organ has prominently high uptake of (18F)OGA-1;
  2. Phase 2: kinetic brain imaging in ten (10) subjects with up to 5 mCi injection to quantify OGA in brain relative to concurrent measurement of the parent radioligand in arterial plasma and venous plasma;
  3. Phase 3: if (18F)OGA-1 is successful in Phase 2 in the first couple of subjects, we will estimate the radiation-absorbed doses by performing whole body imaging on a total of eight (8) subjects, with 5 mCi injection;
  4. Phase 4: test-retest analysis in twelve (12) subjects, of brain binding relative to concurrent measurement of the parent radioligand in arterial plasma (5 mCi per scan) and venous plasma.

Thus, a total of 9 for whole body imaging and 22 for brain imaging

Study Population:

Healthy adult female and male volunteers (n= 22, ages greater than or equal to 18) will undergo brain imaging. An additional nine healthy volunteers will undergo whole body dosimetry analysis, for a total of 31 healthy volunteers.

Design:

For quantification of (18F)OGA-1, 22 healthy controls will undergo brain PET imaging using [18F]OGA-1 an arterial line, and venous line. Of this group of 22 healthy controls having brain PET imaging, twelve of them will have a test-retest scan. Nine additional subjects will have a whole body PET scan for dosimetry. For dosimetry, no arterial line will be used.

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Outcome Measures:

To assess quantitation of OGA with (18F)GA-1, we will primarily use two outcome measures, namely the identifiability and time stability of distribution volume (VT) calculated with compartmental modeling. In the test-retest study, we will calculate the retest variability. We will assess whole-body biodistribution and dosimetry of (18F)OGA-1 by calculating doses to organs and the effective dose to the body as a whole.

Study Type

Observational

Enrollment (Actual)

28

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 100 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Healthy Volunteers

Description

  • 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:

  • Any current Axis I diagnosis, based on interview and self-reporting performed under screening protocol 01-M-0254.
  • Clinically significant laboratory abnormalities, based on tests performed under screening protocol 01-M-0254 that may include: CBC, acute care panel, hepatic panel, mineral panel, UA, urine drug screen, urine HCG (females), vitamin B12, folate, lipid panel, hepatitis panel (A, B, C), RPR, total protein, hs-CRP, uric acid, CK, LDH, thyroid panel, PT/PTT, and EKG.
  • Positive HIV test.
  • Unable to have an MRI scan.
  • History of medical or neurologic illness / 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.
  • NIMH employees/staff and their immediate family members will be excluded from the study per NIMH policy.

Exclusion criteria for the dosimetry subjects are the same as reported above, with the exception of MRI contraindications, because an MRI will not be performed in these subjects.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
1
Healthy Volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The indentifiability and time stability of the distribution volume calculated with compartmental modeling of [F18 OGA-1]. In the test-retest study the retest variability will be calculated.
Time Frame: Ongoing
Ongoing

Secondary Outcome Measures

Outcome Measure
Time Frame
Whole-body distribution and dosimetry of [18F]OGA-1
Time Frame: Ongoing
Ongoing

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 2, 2016

Primary Completion (Actual)

June 25, 2019

Study Completion (Actual)

June 25, 2019

Study Registration Dates

First Submitted

August 14, 2018

First Submitted That Met QC Criteria

August 14, 2018

First Posted (Actual)

August 15, 2018

Study Record Updates

Last Update Posted (Actual)

June 28, 2019

Last Update Submitted That Met QC Criteria

June 27, 2019

Last Verified

June 25, 2019

More Information

Terms related to this study

Other Study ID Numbers

  • 160105
  • 16-M-0105

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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