Competition With Striatal [11C]ORM-13070 Binding by Atipamezole and Endogenous Noradrenaline

Brief Summary

The purpose of this study is to validate \[11C\]ORM-13070 as an alpha2C-adrenoceptor imaging agent for human positron emission tomography (PET) studies of brain alpha2C-adrenoceptor occupancy.

Intervention / Treatment

  • Atipamezole (DRUG)
    Administration of a single dose of 5-150 micrograms of atipamezole as an intravenous infusion
  • Atomoxetine (DRUG)
    A single dose of 1.2 mg/kg of atomoxetine administered orally
  • Ketamine (DRUG)
    A single dose of ketamine (approximately 60 mg) administered as an intravenous infusion
  • Cold pressor test (OTHER)
    30-45 min cold pressor test of the foot
  • Insulin (DRUG)
    Insulin administered as an intravenous infusion to induce hypoglycemia
  • Placebo (DRUG)
    A single dose of placebo (capsules) administered orally

Condition or Disease

  • Healthy

Phase

  • Phase 1
  • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 20 Years to 40 Years
    Enrollment: 10 (ACTUAL)
    Funded by: Other|Industry
    Allocation: Randomized
    Primary Purpose: Basic Science

    Masking

    SINGLE:
    • Participant

    Clinical Trial Dates

    Start date: Sep 01, 2011
    Primary Completion: Jan 01, 2012 ACTUAL
    Completion Date: Jan 01, 2012 ACTUAL
    Study First Posted: Sep 16, 2011 ESTIMATED
    Results First Posted: Aug 31, 2020
    Last Updated: Feb 15, 2013

    Sponsors / Collaborators

    Lead Sponsor: University of Turku
    Responsible Party: N/A

    Participant Groups

    • No description provided

    • No description provided

    • No description provided

    • No description provided

    • No description provided

    • No description provided

    Eligibility Criteria

    Sex: Male
    Minimum Age: 20
    Maximum Age: 40
    Age Groups: Adult
    Healthy Volunteers: Yes

    Inclusion Criteria:

    * Written informed consent (IC) obtained.
    * Good general health ascertained by detailed medical history, laboratory investigations and physical examination.
    * Males between 20 and 40 years of age (inclusive).
    * Body mass index (BMI) between 18-28 kg/m2 inclusive (BMI = weight/height2).
    * Weight 60-100 kg (inclusive).

    Exclusion Criteria:

    * Suspected poor compliance with the protocol or inability to communicate well with the study personnel.
    * Veins unsuitable for repeated venipuncture.
    * CYP2D6 slow metabolizer or ultrarapid metabolizer genotype.
    * Evidence of clinically significant cardiovascular, renal, hepatic, haematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disease as judged by the investigator.
    * Any condition requiring regular concomitant medication including herbal products or likely to need any concomitant medication during the study.
    * Susceptibility to severe allergic reactions.
    * Intake of any medication that could affect the outcome of the study, within 2 weeks prior to the tracer administration (2 months for enzyme inducing drugs like rifampicin or carbamazepine), or less than 5 times the half-life of the medication.
    * Regular consumption of more than 21 units of alcohol per week (1 unit = 4 cl spirits, about 13 g of alcohol).
    * Current use of nicotine-containing products more than 5 cigarettes or equivalent/day.
    * Inability to refrain from using nicotine-containing products during the stay at the study centre.
    * Inability to refrain from consuming caffeine-containing beverages during the stay at the study centre, e.g. propensity for headache when refraining from caffeine-containing beverages.
    * Blood donation or loss of significant amount of blood within 2 months prior to the screening visit.
    * Abnormal 12-lead electrocardiogram (ECG) finding of clinical relevance after 10 minutes rest in supine position at the screening visit, for example:
    * QTc (calculated using Bazett's formula) \> 450 msec,
    * PR \< 120 msec or \> 210 msec,
    * QRS \< 70 msec or \> 120 msec.
    * Heart rate (HR) \< 40 beats/minute or \> 90 beats/minute after 10 minutes rest in supine position at the screening visit.
    * At the screening visit, systolic blood pressure (BP) \< 90 mmHg or \> 140 mmHg after 10 minutes in supine position, diastolic BP \< 50 mmHg or \> 90 mmHg after 10 minutes in supine position.
    * Any abnormal laboratory value, vital sign or physical examination result, which may in the opinion of the investigator interfere with the interpretation of the test results or cause a health risk to the subject if he takes part in the study.
    * History of drug abuse or positive result in drug abuse test.
    * Positive serology to human immunodeficiency virus antibodies (HIVAb), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HCVAb).
    * Anatomical abnormality in brain MRI which may in the opinion of the investigator interfere with the interpretation of the PET results.
    * Any other condition that in the opinion of the investigator would interfere with the evaluation of the results or constitute a health risk to the subject.
    * Participation in another clinical drug study within 3 months prior to this study.
    * Participation in a prior PET study or other medical or occupational exposure to significant doses of ionizing radiation.
    * Any contraindication to MRI of the brain.

    Primary Outcomes
    • PET tracer (interventional drug) uptake in the brain is measured for 30 minutes by PET after various pharmacological and physiological pre-treatments.

    More Details

    NCT Number: NCT01435213
    Acronym: AIMI
    Other IDs: 3099002
    Study URL: https://clinicaltrials.gov/study/NCT01435213
    Last updated: Sep 29, 2023