Cerebral Pharmacodynamic Effects of 5-HT1B Receptor Stimulation
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|ClinicalTrials.gov Identifier: NCT02932488|
Recruitment Status : Terminated (Pilot study with sumatriptan found no significant changes in the primary outcome parameter (change in CBF))
First Posted : October 13, 2016
Last Update Posted : June 27, 2019
|Condition or disease||Intervention/treatment||Phase|
|Healthy Volunteers||Drug: Sumatriptan||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||17 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Cerebral Pharmacodynamic Effects of 5-HT1B Receptor Stimulation|
|Study Start Date :||September 2016|
|Actual Primary Completion Date :||June 2019|
|Actual Study Completion Date :||June 2019|
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.
Sumatriptan is a 5-HT1B receptor agonist used for treatment of migraine attacks
Other Name: Imigran
- Changes in 5-HT1B receptor binding as measured with [11C]AZ10419369 [ Time Frame: 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. ]Both measures of receptor binding will be calculated from the same PET-MR acquisition.
- Changes in cerebral blood flow measured with pseudo continuous Arterial Spin Labeling [ Time Frame: CBF is measured 15 min prior and 30 min after the injection of sumatriptan giving 45 min of total CBF measurement time. ]CBF will be measured continuous and within the acquisition a dynamic change in CBF upon administration of sumatriptan will be obtained.
- Change in [11C]AZ10419369 concentration in blood and plasma [ Time Frame: At 2.5, 20, 49, 51, 90 and 120 min after injection of [11C]AZ10419369 ]Blood samples will be drawn throughout the acquisition time and radioactivity in blood and plasma will be measured.
- Plasma concentration of sumatriptan [ Time Frame: At -1, 1, 10, 20, 35 and 75 min after injection of sumatriptan ]Blood samples will taken to measure the plasma concentration of the drug.
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): NCT02932488
|Neurobiology Research Unit, Rigshospitalet|
|Copenhagen, Denmark, 2100|
|Study Chair:||Gitte M Knudsen, MD, DMSc||Neurobiology Research Unit, Rigshospitalet|