Cerebral Pharmacodynamic Effects of 5-HT1B Receptor Stimulation

Healthy Volunteers Clinical Trial

Official title:

Cerebral Pharmacodynamic Effects of 5-HT1B Receptor Stimulation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02932488
• Other study ID #: NP3
• Status: Terminated
• Phase: Phase 1
• Start date: September 2016
• Est. completion date: June 2019

Study information

• Verified date: June 2019
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Recent technological advances in multimodal imaging have enabled the simultaneous acquisition of magnetic resonance imaging (MRI) and PET data. Whereas functional MRI (fMRI) provides excellent spatio-temporal resolution for localizing changes in brain activity, PET offers high sensitivity and neurochemical specificity. Together, PET and MRI measures have the potential to help clarify the neurochemical basis of changes in fMRI signal induced by selective exogenous ligands or endogenous neurotransmitter.

In the present study we will target the 5-HT1B receptor for which a selective radioligand exist (11C-AZ10419369). The receptor can be stimulated with the agonist sumatriptan, which is used for alleviating migraine attacks. The mechanism of action of sumatriptan is not precisely known and it is unknown to what degree sumatriptan crosses the blood-brain barrier and exerts its effect in the parenchyma. In this study we can determine the blood brain barrier penetration of sumatriptan and thereby evaluate Effect sizes, distribution of signal changes, and correlation between the occupancy at the 5-HT1B receptor in the parenchyma (measured by changes in BPND) and the hemodynamic response (measured by changes in CBF).

Ahead of the main study a pilot study will be conducted in which increasing doses of sumatriptan will be tested in the same subject to obtain a dose-response curve. At the same time side effects will be observed and scored. This serves to find the dose with maximum effect size but minimal side effects, which can then be used in the main study for all subjects.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 17
• Est. completion date: June 2019
• Est. primary completion date: June 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Healthy subjects

• Age 18-60

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

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

Locations

Country	Name	City	State
Denmark	Neurobiology Research Unit, Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Gitte Moos Knudsen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	Change in [11C]AZ10419369 concentration in blood and plasma	Blood samples will be drawn throughout the acquisition time and radioactivity in blood and plasma will be measured.	At 2.5, 20, 49, 51, 90 and 120 min after injection of [11C]AZ10419369
Secondary	Plasma concentration of sumatriptan	Blood samples will taken to measure the plasma concentration of the drug.	At -1, 1, 10, 20, 35 and 75 min after injection of sumatriptan