Cerebral Pharmacodynamic Effects of 5-HT1B Receptor Stimulation

NCT02932488 | Terminated Phase 1 DMC

• 1 other identifier: NP3
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to show that PET-MR imaging can be used for obtaining a pharmacodynamic profile of drugs. By using the 5-HT1B receptor as target we also aim to find effect areas and sizes of the 5-HT1B receptor agonist sumatriptan.

Conditions

Healthy Volunteers

Keywords

PET-MR; 5-HT1B receptor; Sumatriptan; phMRI; [11C]AZ10419369

Outcome Measures

Primary Outcomes (2)

• Changes in 5-HT1B receptor binding as measured with [11C]AZ10419369

  Both measures of receptor binding will be calculated from the same PET-MR acquisition.

  Two binding potentials are obtained from the 120 min scan: Baseline BPND is determined from 0-50 min. Intervention BPND is determined from 50-120 min.

• Changes in cerebral blood flow measured with pseudo continuous Arterial Spin Labeling

  CBF will be measured continuous and within the acquisition a dynamic change in CBF upon administration of sumatriptan will be obtained.

  CBF is measured 15 min prior and 30 min after the injection of sumatriptan giving 45 min of total CBF measurement time.

Secondary Outcomes (2)

• Change in [11C]AZ10419369 concentration in blood and plasma

  At 2.5, 20, 49, 51, 90 and 120 min after injection of [11C]AZ10419369

• Plasma concentration of sumatriptan

  At -1, 1, 10, 20, 35 and 75 min after injection of sumatriptan

Study Arms (1)

Sumatriptan

EXPERIMENTAL

In the pilot study (an MR-only study) subjects will receive up to five doses of sumatriptan in the range of 10 ug/kg to 80 ug/kg. This allows us to establish a dose-response curve for each subject. Administration of sumatriptan in the pilot study will be spaced with approximately one week apart to avoid carry-over effects of the drug. In the main study (a PET-MR study), the sumatriptan dose with the maximal effect size and minimum side effects will be used for all subjects.

Drug: Sumatriptan

Interventions

Sumatriptan DRUG

Sumatriptan is a 5-HT1B receptor agonist used for treatment of migraine attacks

Also known as: Imigran

Sumatriptan

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy subjects
• Age 18-60

You may not qualify if:

• Primary psychiatric disease (DSM IV Axis I or WHO ICD-10 diagnostic classification).
• Present or former neurological diseases,
• Severe somatic disease
• Medication that can interfere with the test results.
• Doesn't speak Danish fluently or is severely, visually or hearing impaired.
• Information regarding former learning disabilities.
• Pregnancy at the time of the scanning
• Breast feeding
• MR-scanner incompatibility (metal in soft tissue)
• Alcohol or drug abuse
• Allergy to ingredients in used drugs
• Participation in experiments with radioactivity (\>10 mSv) within the last year or considerable work-related exposure to radioactivity.

Sponsors & Collaborators

• Gitte Moos Knudsen: lead

Study Sites (1)

Neurobiology Research Unit, Rigshospitalet

Copenhagen, 2100, Denmark

Location

MeSH Terms

Interventions

Sumatriptan

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Gitte M Knudsen, MD, DMSc

  Neurobiology Research Unit, Rigshospitalet

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chair, Professor, MD, DMSc

Study Record Dates

• First Submitted: October 7, 2016
• First Posted: October 13, 2016
• Study Start: September 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: June 27, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)