Title: Evaluation of a Novel PET Radioligand for Phosphodiesterase-4D (PDE4D)

Completed · Phase 1/Phase 2

Conditions studied: Depression

In brief

Background: The brain enzyme phosphodiesterase-4D (PDE4D) may affect thinking and depression. Drugs with some radioactivity can attach to enzymes and be seen on a scan. Researchers want to test a new radioactive drug, 11C-T-1650, to measure PDE4D in the brain and body. They also want to see if the new drug BPN14770 blocks 11C-T-1650 from the brain. They want to learn more about psychiatric disorders and possible treatments. Objectives: To study how well 11C-T-1650 helps show PDE4D on a scan and to see if BPN14770 blocks it. Eligibility: Healthy adults at least 18 years old Design: Participants will be screened in other protocols. Some participants will have 1 body PET scan. Some participants will have 2 brain PET scans and 1 brain MRI within 1 year. Some participants (ages 18 55) will: Have 3 brain PET scans and 1 MRI Take BPN14770 by mouth twice daily for 3 7 days Have blood and urine tests Have a follow-up physical exam and heart test PET (positron emission tomography) scans will take 2 3 hours. Participants will: Have a thin plastic tube (catheter) placed in an arm vein by needle. Get a small amount of 11C-T-1650 injected via catheter. Another catheter may be placed to draw blood. Lie quietly on a bed that slides into a donut-shaped scanner without sleeping. They may get a short break. Have heart and vital signs monitored. Have blood and urine tests. Learn about drinking fluids and urinating after the scan MRI (magnetic resonance imagining) scans will take 30 60 minutes: Participants will lie on a table that slides into a metal cylinder in a magnetic field. Sponsoring Institute: National Institute of Mental Health ...

Key facts

Study ID

NCT03861000

Run by

National Institute of Mental Health (NIMH)

People needed

3

Starts

2019-03-12

Expected to finish

2020-02-11

Last updated by the study team

2021-03-22

Who can join

Age: 18 and older, up to 55. Sex: any. Healthy volunteers: accepted.

You may not qualify if…

• All phases
• Clinically significant laboratory abnormalities based on the following tests (performed under screening protocol 01-M-0254 or 17-M-0181): CBC; acute care panel; hepatic panel; mineral panel; urinalysis; urine drug screen; urine pregnancy test (females); and lipid panel; hepatitis panel (A, B, C); syphilis screening test; total protein; uric acid;creatine kinase; cholesterol; thyroid panel; prothrombin and partial prothrombin tests; and EKG.
• Have a brain disease (such as multiple sclerosis or stroke).
• Any current Axis I diagnosis, based on interview and self-reporting performed under screening protocol 01-M-0254 or 17-M-0181.
• Positive HIV test.
• Current or past history of significant cardiovascular, cerebrovascular, pulmonary, renal, or liver disease. Stable, well-controlled hypertension and hyperlipidemias are allowed.
• Taking psychotropic drugs (i.e. benzodiazepines or antidepressants) including sedative antihistamines; moderate to strong inhibitors or inducers (i.e. fluconazole or ciprofloxacin) of any CYP450 enzyme. A complete listing of such inhibitors or inducers may be found in Attachment 1, List of P450 inhibitors.
• Recent exposure to radiation related to research (e.g., 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.
• Positive screen for drugs of abuse or cotinine (at screen or upon admission), or a positive alcohol result (upon admission).
• Current use of psychiatric medications.
• NIMH employees and staff or immediate family members of NIMH employee/staff.
• Additional exclusion criterial for Phase 2 and 4
• coagulation disorder;
• thrombocytopenia;
• Found to have inadequate collateral circulation of the radial artery
• Are unable to have an MRI scan (e.g., pacemakers or other implanted electrical devices, brain stimulators, dental implants, aneurysm clips (metal clips on the wall of a large artery), metallic prostheses (including metal pins and rods, heart valves, and cochlear implants), permanent eyeliner, implanted delivery pumps, or shrapnel fragments, metal fragments in the eye)
• Additional exclusion criterial for Phase 2
• Marked bradycardia (heart rate 45 beats per minute [bpm]) or tachycardia (heart rate 110 bpm) based on supine ECG values obtained at Screening, before the first dose of BPN14770 on the day of the study. Out-of-range vital signs may be repeated once at each eligibility assessment (prior to the start of dosing).
• History of hematological disorders (e.g., thrombocytopenia) in the immediate family (i.e., parents and siblings).
• Clinically important or significant conduction abnormalities on single ECG (including QTc interval 450 msec) or evidence or history of long QT syndrome. This exclusion applies to the ECGs obtained at Screening, before the first dose of BPN14770 on the day of the study.
• Current or past history of gastric or duodenal ulcers or other diseases of the gastrointestinal tract that could interfere with absorption of study drug. Note: Subjects with a history of appendectomy or cholecystectomy may be enrolled.
• Active acute or chronic infectious diseases.
• Any history of alcohol or drug abuse within the previous year prior to the Screening visit (per the current edition of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5), or regular (daily) consumption of alcohol exceeding two bottles of beer, or the equivalent amount of other forms of alcohol (1 serving = 12 oz beer, 5.0 oz wine, or 1.5 oz distilled spirits).

Where it is running

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

Full record on ClinicalTrials.gov

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