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Changes in Striatal [11C]ORM-13070 Binding Elicited by Changing Levels of Endogenous Noradrenaline (AIMI2)

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ClinicalTrials.gov Identifier: NCT01794975
Recruitment Status : Completed
First Posted : February 20, 2013
Last Update Posted : February 20, 2013
Sponsor:
Collaborators:
Turku University Hospital
Orion Corporation, Orion Pharma
Information provided by (Responsible Party):
Juha Rinne, University of Turku

Brief Summary:
The primary objective of the study is to further investigate whether striatal [11C]ORM-13070 uptake can be reduced by physiological and pharmacological challenges that increase the synaptic concentrations of noradrenaline in the human brain. Each subject will undergo 3 PET scans, a baseline PET scan and two scans with noradrenaline challenges: intravenous administration of ketamine and oral administration of atomoxetine combined with a cold pressor test where the subject's foot is placed in an 8 °C water basin. Eight healthy male subjects will be included in the study.

Condition or disease Intervention/treatment Phase
Changes in Striatal [11C]ORM-13070 Binding. Drug: Ketamine Drug: Atomoxetine Other: Cold pressor test Drug: Placebo Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Changes in Striatal [11C]ORM-13070 Binding Elicited by Changing Levels of Endogenous Noradrenaline - a PET Study in Healthy Human Subjects
Study Start Date : August 2012
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Ketamine
Ketamine will be administered intravenously using a pseudo steady state infusion approach with a target plasma concentration of 300 ng/ml starting 15 minutes before the PET scan and continued throughout the scan.
Drug: Ketamine
Other Name: Ketalar

Drug: Placebo
Active Comparator: Atomoxetine and the cold pressor test
An oral dose of approximately 1.2 mg/kg (range, 1.12-1.26 mg/kg) of atomoxetine is administered 1 h before the PET scans. A cold pressor test is employed as a physiological noradrenergic stimulus. The subject's foot is placed in a 8 °C water basin for the duration of the PET scan.
Drug: Atomoxetine
Other Name: Strattera

Other: Cold pressor test
Other Name: Cold stimulation of the subject's foot

Drug: Placebo
Placebo Comparator: Placebo
Placebo capsules are given to mimic the atomoxetine treatment at each treatment visit except the atomoxetine visit. A baseline PET scan with [11C]ORM-13070 will be performed for all subjects with the placebo treatment only.
Drug: Placebo



Primary Outcome Measures :
  1. Receptor occupancy [ Time Frame: 5-30 minutes ]
    Alpha2C-adrenoceptor occupancy in the striatum will be assessed by comparing the amount of tracer uptake during the control scan to the amount of tracer uptake during the noradrenaline challenges. This assessment will be made once the results of all 3 scans are available for each subject.



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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. Suspected poor compliance with the protocol or inability to communicate well with the study personnel.
  2. Veins unsuitable for repeated venipuncture.
  3. CYP2D6 slow metabolizer or ultrarapid metabolizer genotype.
  4. Evidence of clinically significant cardiovascular, renal, hepatic, haematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric disease as judged by the investigator.
  5. Any condition requiring regular concomitant medication including herbal products or likely to need any concomitant medication during the study.
  6. Susceptibility to severe allergic reactions.
  7. 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.
  8. Regular consumption of more than 21 units of alcohol per week (1 unit = 4 cl spirits, about 13 g of alcohol).
  9. Current use of nicotine-containing products more than 5 cigarettes or equivalent/day.
  10. Inability to refrain from using nicotine-containing products during the stay at the study centre.
  11. 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.
  12. Blood donation or loss of significant amount of blood within 2 months prior to the screening visit.
  13. Abnormal 12-lead electrocardiogram (ECG) finding of clinical relevance after 10 minutes rest in supine position at the screening visit
  14. Heart rate (HR) < 40 beats/minute or > 90 beats/minute after 10 minutes rest in supine position at the screening visit.
  15. 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.
  16. 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.
  17. History of drug abuse or positive result in drug abuse test.
  18. Positive serology to human immunodeficiency virus antibodies (HIVAb), hepatitis B surface antigen (HBsAg) or hepatitis C virus antibodies (HCVAb).
  19. Anatomical abnormality in brain MRI which may in the opinion of the investigator interfere with the interpretation of the PET results.
  20. 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.
  21. Participation in another clinical drug study within 3 months prior to this study.
  22. Participation in a prior PET study or other medical or occupational exposure to significant doses of ionizing radiation.
  23. Any contraindication to MRI of the brain.

Information from the National Library of Medicine

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): NCT01794975


Locations
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Finland
Clinical Research Services Turku (CRST) / Turku PET Centre
Turku, Finland
Sponsors and Collaborators
University of Turku
Turku University Hospital
Orion Corporation, Orion Pharma
Investigators
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Principal Investigator: Juha Rinne, PhD Turku PET Centre
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Responsible Party: Juha Rinne, Professor, MD, PhD, University of Turku
ClinicalTrials.gov Identifier: NCT01794975    
Other Study ID Numbers: AIMI 2
First Posted: February 20, 2013    Key Record Dates
Last Update Posted: February 20, 2013
Last Verified: February 2013
Keywords provided by Juha Rinne, University of Turku:
PET
striatum
receptor occupancy
noradrenaline
alpha2c
Additional relevant MeSH terms:
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Ketamine
Atomoxetine Hydrochloride
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Adrenergic Agents