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

This study has been completed.
Sponsor:
Collaborator:
Orion Corporation, Orion Pharma
Information provided by (Responsible Party):
Juha Rinne, University of Turku
ClinicalTrials.gov Identifier:
NCT01435213
First received: September 14, 2011
Last updated: February 15, 2013
Last verified: February 2013
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Atipamezole
Drug: Atomoxetine
Drug: Ketamine
Other: Cold pressor test
Drug: Insulin
Drug: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Competition With Striatal [11C]ORM-13070 Binding by Atipamezole and Endogenous Noradrenaline - a PET Study in Healthy Human Subjects

Resource links provided by NLM:


Further study details as provided by University of Turku:

Primary Outcome Measures:
  • Receptor occupancy [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]
    PET tracer (interventional drug) uptake in the brain is measured for 30 minutes by PET after various pharmacological and physiological pre-treatments.


Enrollment: 10
Study Start Date: September 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atipamezole Drug: Atipamezole
Administration of a single dose of 5-150 micrograms of atipamezole as an intravenous infusion
Other Name: ANTISEDAN VET
Experimental: Atomoxetine Drug: Atomoxetine
A single dose of 1.2 mg/kg of atomoxetine administered orally
Other Name: Strattera
Experimental: Ketamine Drug: Ketamine
A single dose of ketamine (approximately 60 mg) administered as an intravenous infusion
Other Name: Ketalar
Experimental: Insulin-induced hypoglycemia Drug: Insulin
Insulin administered as an intravenous infusion to induce hypoglycemia
Other Name: Insulin Actrapid
Experimental: Cold pressor test Other: Cold pressor test
30-45 min cold pressor test of the foot
Experimental: Placebo Drug: Placebo
A single dose of placebo (capsules) administered orally

  Eligibility

Ages Eligible for Study:   20 Years to 40 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01435213

Locations
Finland
University of Turku, Clinical Research Services Turku CRST
Turku, Finland, 20520
University of Turku, Turku PET Centre
Turku, Finland, 20520
Sponsors and Collaborators
University of Turku
Orion Corporation, Orion Pharma
Investigators
Principal Investigator: Juha Rinne, MD, PhD University of Turku
  More Information

Additional Information:
No publications provided

Responsible Party: Juha Rinne, Professor, University of Turku
ClinicalTrials.gov Identifier: NCT01435213     History of Changes
Other Study ID Numbers: 3099002
Study First Received: September 14, 2011
Last Updated: February 15, 2013
Health Authority: Finland: Ethics Committee
Finland: Finnish Medicines Agency

Keywords provided by University of Turku:
alpha2-adrenoceptor
receptor occupancy
positron emission tomography
[11C]ORM-13070
striatum
brain
noradrenaline
norepinephrine
endogenous
binding
Validation studies

Additional relevant MeSH terms:
Ketamine
Norepinephrine
Atipamezole
Atomoxetine
Insulin
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Hypoglycemic Agents
Sympathomimetics
Autonomic Agents
Vasoconstrictor Agents
Cardiovascular Agents
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Adrenergic alpha-2 Receptor Antagonists

ClinicalTrials.gov processed this record on July 26, 2014