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

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ClinicalTrials.gov Identifier: NCT03861000
Recruitment Status : Recruiting
First Posted : March 4, 2019
Last Update Posted : May 22, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:

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

...


Condition or disease Intervention/treatment Phase
Depression Drug: [C-11]T-1650 Drug: BPN14770 Phase 1

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Evaluation of a Novel PET Radioligand for Phosphodiesterase-4D (PDE4D)
Actual Study Start Date : March 12, 2019
Estimated Primary Completion Date : March 11, 2022
Estimated Study Completion Date : December 7, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1
Healthy Controls
Drug: [C-11]T-1650
radio-labeled drug

Drug: BPN14770
selective compound




Primary Outcome Measures :
  1. Binding of [C-11]T-1650 and binding site occupancy of BPN14770 [ Time Frame: 3 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

All phases

  1. Age greater than equal 18.
  2. Able to give written informed consent.
  3. Medically and psychiatrically healthy.
  4. Enrolled in 01-M-0254 The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers (PI: Dr. Carlos Zarate) or 17-M-0181 Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies (PI: Dr. Joyce Chung).

Additional inclusion criterial for Phase 2

  1. Age less than or equal to 55.
  2. Body mass index between 18 kg/m2 to 32 kg/m2, inclusive, and body weight of greater than equal 50 kg (110 pounds).
  3. Female subjects must be surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months prior to dosing of BPN14770), at least two years post-menopausal, or willing to use two barrier methods of contraception from initial screening until one month after taking the last dose of study drug.
  4. Male subjects must be willing to inform female partners of their participation in the study and must agree to use adequate contraceptive methods (vasectomy performed at least 6 months prior to dosing BPN14770 or use at least one barrier method of birth control).

EXCLUSION CRITERIA:

All phases

  1. 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.
  2. Have a brain disease (such as multiple sclerosis or stroke).
  3. Any current Axis I diagnosis, based on interview and self-reporting performed under screening protocol 01-M-0254 or 17-M-0181.
  4. Positive HIV test.
  5. Current or past history of significant cardiovascular, cerebrovascular, pulmonary, renal, or liver disease. Stable, well-controlled hypertension and hyperlipidemias are allowed.
  6. 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.
  7. 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.
  8. Inability to lie flat on camera bed for at least two hours.
  9. Pregnancy or breastfeeding.
  10. Positive screen for drugs of abuse or cotinine (at screen or upon admission), or a positive alcohol result (upon admission).
  11. Current use of psychiatric medications.
  12. NIMH employees and staff or immediate family members of NIMH employee/staff.

Additional exclusion criterial for Phase 2 and 4

  1. coagulation disorder;
  2. thrombocytopenia;
  3. Found to have inadequate collateral circulation of the radial artery
  4. 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

  1. 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).
  2. History of hematological disorders (e.g., thrombocytopenia) in the immediate family (i.e., parents and siblings).
  3. 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.
  4. 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.
  5. Active acute or chronic infectious diseases.
  6. 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).
  7. Unwilling to abstain from alcohol within 72 hours of before the first dose of BPN14770.
  8. Currently ingest nicotine in any way (including smoking cigarettes, vaping, and via patch), or have ingested any nicotine products within the past 3 months.
  9. Participation in other clinical studies involving investigational drug within the previous 30 days prior to the first day of the study.
  10. Unwilling to forgo donation of blood or blood products (including plasma) during the 8 weeks before the first day of the study.
  11. History of allergy to penicillin or sulfonamides, or any other clinically significant drug allergy that includes symptoms such as shortness of breath, rash, or edema.
  12. A suicidal ideation intensity score of 2 or higher per screening C-SSRS assessment and/or any suicidal behavior within the past 30 days.

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): NCT03861000


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

Locations
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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 Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Robert B Innis, M.D. National Institute of Mental Health (NIMH)

Additional Information:
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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT03861000     History of Changes
Other Study ID Numbers: 190064
19-M-0064
First Posted: March 4, 2019    Key Record Dates
Last Update Posted: May 22, 2019
Last Verified: May 7, 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
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) ):
Healthy Control Subjects
PET Imaging
Receptor Occupancy
Depression

Additional relevant MeSH terms:
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Depression
Behavioral Symptoms