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

NCT ID: NCT01435213

Last Updated: 2013-02-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2012-01-31

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.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Atipamezole

Group Type: EXPERIMENTAL

Atipamezole

Intervention Type: DRUG

Administration of a single dose of 5-150 micrograms of atipamezole as an intravenous infusion

Atomoxetine

Group Type: EXPERIMENTAL

Atomoxetine

Intervention Type: DRUG

A single dose of 1.2 mg/kg of atomoxetine administered orally

Ketamine

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

A single dose of ketamine (approximately 60 mg) administered as an intravenous infusion

Insulin-induced hypoglycemia

Group Type: EXPERIMENTAL

Insulin

Intervention Type: DRUG

Insulin administered as an intravenous infusion to induce hypoglycemia

Cold pressor test

Group Type: EXPERIMENTAL

Cold pressor test

Intervention Type: OTHER

30-45 min cold pressor test of the foot

Placebo

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

A single dose of placebo (capsules) administered orally

Interventions

Atipamezole

Administration of a single dose of 5-150 micrograms of atipamezole as an intravenous infusion

Intervention Type: DRUG

Atomoxetine

A single dose of 1.2 mg/kg of atomoxetine administered orally

Intervention Type: DRUG

Ketamine

A single dose of ketamine (approximately 60 mg) administered as an intravenous infusion

Intervention Type: DRUG

Cold pressor test

30-45 min cold pressor test of the foot

Intervention Type: OTHER

Insulin

Insulin administered as an intravenous infusion to induce hypoglycemia

Intervention Type: DRUG

Placebo

A single dose of placebo (capsules) administered orally

Intervention Type: DRUG

Other Intervention Names

ANTISEDAN VET; Strattera; Ketalar; Insulin Actrapid

Eligibility Criteria

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.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Orion Corporation, Orion Pharma

INDUSTRY

Sponsor Role: collaborator

University of Turku

OTHER

Sponsor Role: lead

Responsible Party

Juha Rinne

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Juha Rinne, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Turku

Locations

University of Turku, Clinical Research Services Turku CRST

Turku, , Finland

University of Turku, Turku PET Centre

Turku, , Finland

Countries

Finland

Related Links

http://www.crst.fi

Clinical Research Services Turku CRST

http://www.turkupetcentre.fi/

Turku PET Centre

Other Identifiers

3099002

Identifier Type: -

Identifier Source: org_study_id