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

NCT01435213 | Completed Phase 1

• 1 other identifier: 3099002
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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

Keywords

alpha2-adrenoceptor; receptor occupancy; positron emission tomography; [11C]ORM-13070; striatum; brain; noradrenaline; norepinephrine; endogenous; binding; Validation studies

Outcome Measures

Primary Outcomes (1)

• Receptor occupancy

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

  30 minutes

Study Arms (6)

Atipamezole

EXPERIMENTAL

Drug: Atipamezole

Atomoxetine

EXPERIMENTAL

Drug: Atomoxetine

Ketamine

EXPERIMENTAL

Drug: Ketamine

Insulin-induced hypoglycemia

EXPERIMENTAL

Drug: Insulin

Cold pressor test

EXPERIMENTAL

Other: Cold pressor test

Placebo

EXPERIMENTAL

Drug: Placebo

Interventions

Atipamezole DRUG

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

Also known as: ANTISEDAN VET

Atipamezole

Atomoxetine DRUG

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

Also known as: Strattera

Atomoxetine

Ketamine DRUG

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

Also known as: Ketalar

Ketamine

Cold pressor test OTHER

30-45 min cold pressor test of the foot

Cold pressor test

Insulin DRUG

Insulin administered as an intravenous infusion to induce hypoglycemia

Also known as: Insulin Actrapid

Insulin-induced hypoglycemia

Placebo DRUG

A single dose of placebo (capsules) administered orally

Placebo

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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,

Sponsors & Collaborators

• University of Turku: lead
• Orion Corporation, Orion Pharma: collaborator

Study Sites (2)

University of Turku, Clinical Research Services Turku CRST

Turku, 20520, Finland

Location

University of Turku, Turku PET Centre

Turku, 20520, Finland

Location

Related Links

• Clinical Research Services Turku CRST
• Turku PET Centre

MeSH Terms

Interventions

atipamezole; Atomoxetine Hydrochloride; Ketamine; Insulin; insulin, neutral

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Juha Rinne, MD, PhD

  University of Turku

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: September 14, 2011
• First Posted: September 16, 2011
• Study Start: September 1, 2011
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: February 18, 2013

Record last verified: 2013-02

Locations

FI (2)