Changes in Striatal [11C]ORM-13070 Binding.Phase 1AIMI2NCT01794975
Changes in Striatal [11C]ORM-13070 Binding Elicited by Changing Levels of Endogenous Noradrenaline
A Phase 1 study testing Ketamine, Atomoxetine and Cold pressor test in people with Changes in Striatal [11C]ORM-13070 Binding., run by University of Turku at 1 site in Finland.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 40 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Changes in Striatal [11C]ORM-13070 Binding.
- What is being tested?
- Ketamine, Atomoxetine and Cold pressor test
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteFinland
- Study dates
- Aug 2012to Dec 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 40 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
- Weight 60-100 kg (inclusive).
Who cannot join
- 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.
Show all 23Show fewer
- 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
- 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.
Trial locations and contacts
1 site in 1 country.
Finland1 site
Clinical Research Services Turku (CRST) / Turku PET Centre
Turku
About this study
Official title: Changes in Striatal [11C]ORM-13070 Binding Elicited by Changing Levels of Endogenous Noradrenaline - a PET Study in Healthy Human Subjects
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.
Read the detailed description
Objectives
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 the endogenous alpha2C-adrenoceptor agonist, noradrenaline, in the human brain.
Methodology
PET will be used to study the effects of two different noradrenaline challenges on the striatal uptake of the novel alpha2C-adrenoceptor imaging agent, [11C]ORM-13070. Each of the eight study subjects will undergo one baseline PET scan without any pretreatment and two scans with two different noradrenaline challenges: i.v. infusion of ketamine and a single oral dose of atomoxetine combined with cold pressor test. The sequence of the baseline scan and the other scans for each subject will be based on balanced randomization. Double-blind administration of the pretreatments will not be possible, but the PET scanning data will be analyzed by a person who is not aware of the treatment identity. Venous blood samples will be collected for determination of concentrations of the [11C]ORM-13070 tracer and its radioactive metabolites, the test drugs atomoxetine and ketamine, and endogenous noradrenaline as a biomarker of the employed challenges. Blood pressure and heart rate will be measured as physiological indicators of sympathetic activation. Subject safety will be monitored by vital signs, questioning and clinical observation. The binding potential of the tracer in the striatum at baseline will be compared with the tracer binding potential after each of the noradrenaline challenges.
Sample size
Eight healthy male subjects will be included in the study. Discontinued subjects may be replaced by new subjects as decided by the Principal Investigator
Duration of treatment
After the screening visit, there will be an interval of no more than 45 days before the first PET visit. Each subject will undergo 3 PET scans: a baseline PET scan, and two scans with noradrenaline challenges. The PET experiments of each subject will be separated by intervals of at least 5 days. An end-of-study visit will take place within 21 days after the last PET scan.
Assessments
Efficacy: Alpha2C-adrenoceptor occupancy in the caudate nucleus and putamen will be assessed using the PET imaging agent [11C]ORM-13070 after the administration of two noradrenaline challenges, ketamine and atomoxetine combined with the cold pressor test. Differences in striatal receptor occupancy of the tracer will be assessed using established reference tissue models and the binding potentials of the non-displaceable compartment (BPND) according to the equation: Occupancy = [(BPND bl - BPND challenge) / BPNDbl x 100%]. Plasma noradrenaline concentrations will be measured as a biochemical biomarker before and after the interventions to validate the employed noradrenaline challenges. Blood pressure and heart rate will be used as physiological biomarkers.
Safety: Vital signs, subjective symptoms and ECG will be monitored during the PET visits. Subjects will remain at the study center for a minimum of 4 h after each PET scan, after which the subject will be discharged based on clinical evaluation with a safety check list.
Pharmacokinetics: Venous blood samples will be collected for determination of concentrations of the [11C]ORM-13070 tracer and its radioactive metabolites, and the pretreatment agents atomoxetine and ketamine at pre-defined time points in order to provide information on the fraction of intact tracer in blood and to document the exposure to the pharmacological agents during the PET scans. No formal pharmacokinetic calculations will be performed.
Statistical methods:
Efficacy, safety and pharmacokinetics: Differences in striatal [11C]ORM-13070 uptake between the baseline condition and the different pretreatments will be considered a primary outcome variable and statistical analysis will be carried out with analysis of variance. Descriptive statistical analysis of the tracer fractions in blood during the scans and the concentrations of the employed pretreatment agents will be carried out. Demographic and other baseline data, laboratory safety determinations, physical examination, BP, HR, ECG, AEs and concomitant treatments will be summarised with descriptive statistics or listed.
- Being tested
- Ketamine, Atomoxetine, Cold pressor test, Placebo
- Keywords
- PET, striatum, receptor occupancy, noradrenaline, alpha2c
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar
AtomoxetineDrug
Also called Strattera
Cold pressor testOther
Also called Cold stimulation of the subject's foot
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Active comparator | 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. Receives: Drug: Ketamine; Drug: Placebo |
| Atomoxetine and the cold pressor test | Active comparator | 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. Receives: Drug: Atomoxetine; Other: Cold pressor test; Drug: Placebo |
| Placebo | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Receptor occupancy
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.
Measured: 5-30 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2013 (estimated)
- Study startAug 2012
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Changes in Striatal [11C]ORM-13070 Binding.Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Turku
- Sponsor type
- University, hospital or other
- Collaborators
- Turku University Hospital, Orion Corporation, Orion Pharma
- Responsible party
- Principal investigator, Juha Rinne, University of Turku
- Investigators
- Juha Rinne, PhD, Principal investigator, Turku PET Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01794975
- Sponsor's protocol ID
- AIMI 2
- Acronym
- AIMI2
- Status last verified
- Feb 2013
- First submitted
- 15 Feb 2013
- Last updated
- 20 Feb 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Changes in Striatal [11C]ORM-13070 Binding Elicited by Changing Levels of Endogenous Noradrenaline - a PET Study in Healthy Human Subjects
- ClinicalTrials.gov ID
- NCT01794975
- Acronym / sponsor ID
- AIMI2 / AIMI 2
- Keywords
- PET, striatum, receptor occupancy, noradrenaline, alpha2c
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of TurkuUniversity, hospital or other
- Collaborators
- Turku University Hospital, Orion Corporation, Orion Pharma
- Study start
- Aug 2012
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 20 Feb 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Objectives
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 the endogenous alpha2C-adrenoceptor agonist, noradrenaline, in the human brain.
Methodology
PET will be used to study the effects of two different noradrenaline challenges on the striatal uptake of the novel alpha2C-adrenoceptor imaging agent, [11C]ORM-13070. Each of the eight study subjects will undergo one baseline PET scan without any pretreatment and two scans with two different noradrenaline challenges: i.v. infusion of ketamine and a single oral dose of atomoxetine combined with cold pressor test. The sequence of the baseline scan and the other scans for each subject will be based on balanced randomization. Double-blind administration of the pretreatments will not be possible, but the PET scanning data will be analyzed by a person who is not aware of the treatment identity. Venous blood samples will be collected for determination of concentrations of the [11C]ORM-13070 tracer and its radioactive metabolites, the test drugs atomoxetine and ketamine, and endogenous noradrenaline as a biomarker of the employed challenges. Blood pressure and heart rate will be measured as physiological indicators of sympathetic activation. Subject safety will be monitored by vital signs, questioning and clinical observation. The binding potential of the tracer in the striatum at baseline will be compared with the tracer binding potential after each of the noradrenaline challenges.
Sample size
Eight healthy male subjects will be included in the study. Discontinued subjects may be replaced by new subjects as decided by the Principal Investigator
Duration of treatment
After the screening visit, there will be an interval of no more than 45 days before the first PET visit. Each subject will undergo 3 PET scans: a baseline PET scan, and two scans with noradrenaline challenges. The PET experiments of each subject will be separated by intervals of at least 5 days. An end-of-study visit will take place within 21 days after the last PET scan.
Assessments
Efficacy: Alpha2C-adrenoceptor occupancy in the caudate nucleus and putamen will be assessed using the PET imaging agent [11C]ORM-13070 after the administration of two noradrenaline challenges, ketamine and atomoxetine combined with the cold pressor test. Differences in striatal receptor occupancy of the tracer will be assessed using established reference tissue models and the binding potentials of the non-displaceable compartment (BPND) according to the equation: Occupancy = [(BPND bl - BPND challenge) / BPNDbl x 100%]. Plasma noradrenaline concentrations will be measured as a biochemical biomarker before and after the interventions to validate the employed noradrenaline challenges. Blood pressure and heart rate will be used as physiological biomarkers.
Safety: Vital signs, subjective symptoms and ECG will be monitored during the PET visits. Subjects will remain at the study center for a minimum of 4 h after each PET scan, after which the subject will be discharged based on clinical evaluation with a safety check list.
Pharmacokinetics: Venous blood samples will be collected for determination of concentrations of the [11C]ORM-13070 tracer and its radioactive metabolites, and the pretreatment agents atomoxetine and ketamine at pre-defined time points in order to provide information on the fraction of intact tracer in blood and to document the exposure to the pharmacological agents during the PET scans. No formal pharmacokinetic calculations will be performed.
Statistical methods:
Efficacy, safety and pharmacokinetics: Differences in striatal [11C]ORM-13070 uptake between the baseline condition and the different pretreatments will be considered a primary outcome variable and statistical analysis will be carried out with analysis of variance. Descriptive statistical analysis of the tracer fractions in blood during the scans and the concentrations of the employed pretreatment agents will be carried out. Demographic and other baseline data, laboratory safety determinations, physical examination, BP, HR, ECG, AEs and concomitant treatments will be summarised with descriptive statistics or listed.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Active comparator | Drug: Ketamine, Drug: PlaceboKetamine 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. |
| Atomoxetine and the cold pressor test | Active comparator | Drug: Atomoxetine, Other: Cold pressor test, Drug: PlaceboAn 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. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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. |
Who may qualify
- Ages
- 20 to 40 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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).
- Weight 60-100 kg (inclusive).
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: Ketalar | Drug | Ketamine |
| AtomoxetineAlso: Strattera | Drug | Atomoxetine and the cold pressor test |
| Cold pressor testAlso: Cold stimulation of the subject's foot | Other | Atomoxetine and the cold pressor test |
| Placebo | Drug | Atomoxetine and the cold pressor test, Ketamine, Placebo |
Primary outcome
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2013.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juha Rinne, PhD principal investigator
Turku PET Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketamine, Atomoxetine and Cold pressor test in people with Changes in Striatal [11C]ORM-13070 Binding., run by University of Turku at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Feb 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Receptor occupancy (time frame: 5-30 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Feb 2013; AzTrials last refreshed its copy on 1 Nov 2026.