SchizophreniaNCT03223844
Influence of Amphetamine-induced Sensitization on Dopamine Synthesis and Release
A study testing Dextroamphetamine Sulfate in people with Schizophrenia and Psychosis, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Patients with schizophrenia show enhanced dopamine synthesis capacity and release, an effect that can be evoked in healthy subjects by repeated amphetamine administration. Therefore for the first time the relationship between dopamine synthesis and release will be studied in healthy subjects before and after… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia, Psychosis, Sensitisation
- What is being tested?
- Dextroamphetamine Sulfate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteAustria
- Study dates
- 1 Jan 2018to Dec 2021
- Phase
- Interventional
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males and females aged 18-65, in good general health based on history and physical examination
- Psychiatrically healthy as determined by the Mini-International Neuropsychiatric Interview (M.I.N.I.PLUS) (94))
- No relevant abnormalities in laboratory screening including thyroid function tests, blood cell count, serum electrolytes, liver and kidney function, and urinalysis
- No clinically relevant findings in electrocardiography (ECG)
- No clinically relevant findings in vital signs (blood pressure and pulse)
- No regular use of illegal drugs or alcohol abuse based on declared history and confirmed by urine drug screening
- No history of repeated AMPH (AMPH), cocaine or other stimulant drug use
Who cannot join
- Evidence of present psychiatric or neurological illness according to M.I.N.I.-Plus (any personal or first-degree relative history of: schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, and substance dependence)
- Recreational use of psychostimulant drugs in the past two years; lifetime use of psychostimulants exceeding five exposures
- Medically significant biochemical or hematological abnormality on screening laboratory studies
- Women of childbearing potential: Current pregnancy or breast-feeding
- Clinically relevant abnormalities in the electro-cardiogram (ECG)
- History of myocardial infarction or angina pectoris
Show all 18Show fewer
- Positive urine drug screen within one week prior to PET study day
- Presence of ferromagnetic metal in the body or heart pacemaker
- Claustrophobia
- Any history of arterial hypertension or paroxysmal hypertensive states
- Established diagnosis of advanced arteriosclerosis
- Established diagnosis of hyperthyroidism
- History of hypersensitivity to sympathomimetics
- History of head trauma resulting in loss of consciousness that required medical intervention
- Lifetime history of substance dependence (except nicotine)
- If participation in this study would exceed the annual radiation dose limits (30 mSv) for human subjects
- Subjects currently participating in research studies
- Suicidal ideation or likelihood of a suicide or homicide attempt
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Medical University of Vienna
Vienna, 1090
Ana Weidenauer, MD, 0043140400 ext. 35470, ana.weidenauer@meduniwien.ac.at
About this study
Official title: Disentangling Pre- and Postsynaptic Aspects of Amphetamine-induced Sensitization: a Combined [18F]DOPA / [11C]-(+)-PHNO PET Study
Patients with schizophrenia show enhanced dopamine synthesis capacity and release, an effect that can be evoked in healthy subjects by repeated amphetamine administration. Therefore for the first time the relationship between dopamine synthesis and release will be studied in healthy subjects before and after amphetamine sensitization in order to better understand adaptive mechanisms of the dopamine system.
Read the detailed description
Positron emission tomography (PET) studies have consistently shown increased brain dopamine (DA) synthesis and enhanced d-amphetamine-induced DA release in patients with schizophrenia. Repeated administration of d-amphetamine leads to an increased subjective and behavioral drug-response. This effect, termed "sensitization", is paralleled by an increase in dopamine release to levels akin to those observed in schizophrenia. Schizophrenia thus goes along with a state of 'natural sensitization' towards amphetamines. However, while it is known that DA synthesis and release are both enhanced in schizophrenia, it is unknown whether sensitization changes indices of presynaptic DA synthesis in the striatum of healthy subjects. Thus, for the first time, this project will study the effects of repeated d-amphetamine on uptake of the DA precursor [18F]FDOPA and on d-amphetamine-induced changes in binding of the D2/3 receptor agonist radioligand [11C]-(+)PHNO in a within-subject design. Before and after amphetamine sensitization by repeated intermittent administration subjects will receive an [18F]FDOPA and and a [11C]-(+)PHNO PET scan. For the investigation of the influence of functional and structural cortical properties on dopamine synthesis and release, functional and structural magnet resonance imaging will be performed before and after sensitization.
- Conditions
- Schizophrenia, Psychosis, Sensitisation
- Being tested
- Dextroamphetamine Sulfate
- Keywords
- Dopamine, Amphetamine, Positron Emission Tomography, Magnetic Resonance Imaging, Schizophrenia, Psychosis, [18F]FDOPA, [11C]-(+)-PHNO
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dextroamphetamine SulfateDrug
Also called [11C]-(+)-PHNO PET, [18F]FDOPA PET
Repeated oral administration of dexamphetamine 0.4mg/KG bodyweight four times.
| Study group | Role | What they receive |
|---|---|---|
| Healthy subjects | Experimental | Measurement of Dextroamphetamine Sulfate-induced dopamine release and synthesis before and after amphetamine sensitization. Receives: Drug: Dextroamphetamine Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
[18F]FDOPA Ki values
Relative change in regional [18F]FDOPA Ki values after AMPH sensitization
Measured: Baseline and 2 weeks after amphetamine sensitization, Week 1 and Week 4
Secondary outcomes (11)
[11C]-(+)-PHNO BPND values
Relative change in regional [11C]-(+)-PHNO BPND values after AMPH administration before and after sensitization
Measured: Baseline and 2 weeks after amphetamine sensitization, Week 1 and Week 4
Subjective ratings of amphetamine effects (Drug Effects Questionnaire)
Subjective ratings will be assessed via questionnaire (Drug Effects Questionnaire) four times throughout the study.
Measured: Baseline, after i.v. amphetamine during PHNO PET, on each of the two sensitization visits and 2 weeks after amphetamine sensitization during PHNO PET scanning over the course of 4 weeks. Time points: Week 1 Week 2 Week 4
Subjective ratings of amphetamine effects (Subjective States Questionnaire)
Subjective ratings will be assessed via questionnaire (Subjective States Questionnaire) four times throughout the study.
Measured: Baseline, after i.v. amphetamine during PHNO PET, on each of the two sensitization visits and 2 weeks after amphetamine sensitization during PHNO PET scanning over the course of 4 weeks. Time points: Week 1 Week 2 Week 4
Cognitive measures
Working memory, reward processing and impulsivity will be assessed via a computerized test battery four times throughout the study
Measured: At baseline, on each of the two sensitization visits after amphetamine administration and 2 weeks after amphetamine sensitization before FDOPA scanning, total timeframe 4 weeks, Time points: Week 1 Week 2 Week 4
Impulsiveness
The personality traits impulsiveness will be assessed once during study participation by the questionnaire Barrat Impulsiveness Scale (BIS).
Measured: Baseline, Week 1
Personality-related markers
Personality traits like novelty seeking will be assessed once during study participation using the Temperament and Character Inventory (TCI).
Measured: Baseline, Week 1
Peripheral markers of sensitization
Plasma concentration of the dopamine metabolite HVA, glucose and insulin metabolism related parameters (glucose, glucagon, insulin, c-peptide, somatostatin), plasma cocaine and AMPH-regulated transcript (CART) levels will be measured at each PET study day.
Measured: Baseline FDOPA scan, baseline PHNO + amphetamine scan, post-sensitization PHNO+ amphetamine scan, post-sensitization FDOPA scan, Time points: Week 1 Week 2 Week 4
Salivary cortisol
Salivary cortisol will be assessed using Salivettes ®.
Measured: Salivary cortisol will be assessed each time amphetamine is administered: At baseline and 30, 60, 90, 145 and 210 minutes after i.v. or oral amphetamine administration.
Fractional anisotropy (diffusion-weighted tensor imaging) of white matter
Fractional anisotropy of white matter will be measured by means of magnet resonance imaging.
Measured: Before and after amphetamine sensitization, Week 1, Week 5
Gray matter volume
Gray matter volume will be measured by means of magnet resonance imaging. T1 and PD sequences will be recorded.
Measured: Before and after amphetamine sensitization, Week 1, Week 5
Functional connectivity
Functional connectivity between brain regions will be measured by means of magnet resonance imaging during a resting state of the subject.
Measured: Before and after amphetamine sensitization, Week 1, Week 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start1 Jan 2018
- Primary completionAug 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ana Weidenauer, Medical University of Vienna
- Investigators
- Ana Weidenauer, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03223844
- Sponsor's protocol ID
- 16969
- Status last verified
- Apr 2018
- First submitted
- 8 Jul 2017
- Last updated
- 19 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Weidenauer A, Bauer M, Sauerzopf U, Bartova L, Praschak-Rieder N, Sitte HH, Kasper S, Willeit M. Making Sense of: Sensitization in Schizophrenia. Int J Neuropsychopharmacol. 2016 Dec 31;20(1):1-10. doi: 10.1093/ijnp/pyw081. Print 2017 Jan.
PubMed 27613293Sauerzopf U, Sacco R, Novarino G, Niello M, Weidenauer A, Praschak-Rieder N, Sitte H, Willeit M. Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence. Eur J Neurosci. 2017 Jan;45(1):45-57. doi: 10.1111/ejn.13418. Epub 2016 Oct 19.
PubMed 27690184
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Disentangling Pre- and Postsynaptic Aspects of Amphetamine-induced Sensitization: a Combined [18F]DOPA / [11C]-(+)-PHNO PET Study
- ClinicalTrials.gov ID
- NCT03223844
- Acronym / sponsor ID
- 16969
- Conditions
- Schizophrenia, Psychosis, Sensitisation
- Keywords
- Dopamine, Amphetamine, Positron Emission Tomography, Magnetic Resonance Imaging, Schizophrenia, Psychosis, [18F]FDOPA, [11C]-(+)-PHNO
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- Aug 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 21 Jul 2017 (actual)
- 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.
Patients with schizophrenia show enhanced dopamine synthesis capacity and release, an effect that can be evoked in healthy subjects by repeated amphetamine administration. Therefore for the first time the relationship between dopamine synthesis and release will be studied in healthy subjects before and after amphetamine sensitization in order to better understand adaptive mechanisms of the dopamine system.
Detailed description
Positron emission tomography (PET) studies have consistently shown increased brain dopamine (DA) synthesis and enhanced d-amphetamine-induced DA release in patients with schizophrenia. Repeated administration of d-amphetamine leads to an increased subjective and behavioral drug-response. This effect, termed "sensitization", is paralleled by an increase in dopamine release to levels akin to those observed in schizophrenia. Schizophrenia thus goes along with a state of 'natural sensitization' towards amphetamines. However, while it is known that DA synthesis and release are both enhanced in schizophrenia, it is unknown whether sensitization changes indices of presynaptic DA synthesis in the striatum of healthy subjects. Thus, for the first time, this project will study the effects of repeated d-amphetamine on uptake of the DA precursor [18F]FDOPA and on d-amphetamine-induced changes in binding of the D2/3 receptor agonist radioligand [11C]-(+)PHNO in a within-subject design. Before and after amphetamine sensitization by repeated intermittent administration subjects will receive an [18F]FDOPA and and a [11C]-(+)PHNO PET scan. For the investigation of the influence of functional and structural cortical properties on dopamine synthesis and release, functional and structural magnet resonance imaging will be performed before and after sensitization.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Healthy subjects | Experimental | Drug: Dextroamphetamine SulfateMeasurement of Dextroamphetamine Sulfate-induced dopamine release and synthesis before and after amphetamine sensitization. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Males and females aged 18-65, in good general health based on history and physical examination
- Psychiatrically healthy as determined by the Mini-International Neuropsychiatric Interview (M.I.N.I.PLUS) (94))
- No relevant abnormalities in laboratory screening including thyroid function tests, blood cell count, serum electrolytes, liver and kidney function, and urinalysis
- No clinically relevant findings in electrocardiography (ECG)
- No clinically relevant findings in vital signs (blood pressure and pulse)
Key exclusion criteria (18 listed)
- Evidence of present psychiatric or neurological illness according to M.I.N.I.-Plus (any personal or first-degree relative history of: schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, and substance dependence)
- Recreational use of psychostimulant drugs in the past two years; lifetime use of psychostimulants exceeding five exposures
- Medically significant biochemical or hematological abnormality on screening laboratory studies
- Women of childbearing potential: Current pregnancy or breast-feeding
- Clinically relevant abnormalities in the electro-cardiogram (ECG)
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 |
|---|---|---|
| Dextroamphetamine SulfateAlso: [11C]-(+)-PHNO PET, [18F]FDOPA PETRepeated oral administration of dexamphetamine 0.4mg/KG bodyweight four times. | Drug | Healthy subjects |
Primary outcome
[18F]FDOPA Ki values
Time frame: Baseline and 2 weeks after amphetamine sensitization, Week 1 and Week 4
Relative change in regional [18F]FDOPA Ki values after AMPH sensitization
11 secondary outcomes
[11C]-(+)-PHNO BPND values
Time frame: Baseline and 2 weeks after amphetamine sensitization, Week 1 and Week 4
Subjective ratings of amphetamine effects (Drug Effects Questionnaire)
Time frame: Baseline, after i.v. amphetamine during PHNO PET, on each of the two sensitization visits and 2 weeks after amphetamine sensitization during PHNO PET scanning over the course of 4 weeks. Time points: Week 1 Week 2 Week 4
Subjective ratings of amphetamine effects (Subjective States Questionnaire)
Time frame: Baseline, after i.v. amphetamine during PHNO PET, on each of the two sensitization visits and 2 weeks after amphetamine sensitization during PHNO PET scanning over the course of 4 weeks. Time points: Week 1 Week 2 Week 4
Cognitive measures
Time frame: At baseline, on each of the two sensitization visits after amphetamine administration and 2 weeks after amphetamine sensitization before FDOPA scanning, total timeframe 4 weeks, Time points: Week 1 Week 2 Week 4
Impulsiveness
Time frame: Baseline, Week 1
Personality-related markers
Time frame: Baseline, Week 1
Peripheral markers of sensitization
Time frame: Baseline FDOPA scan, baseline PHNO + amphetamine scan, post-sensitization PHNO+ amphetamine scan, post-sensitization FDOPA scan, Time points: Week 1 Week 2 Week 4
Salivary cortisol
Time frame: Salivary cortisol will be assessed each time amphetamine is administered: At baseline and 30, 60, 90, 145 and 210 minutes after i.v. or oral amphetamine administration.
Fractional anisotropy (diffusion-weighted tensor imaging) of white matter
Time frame: Before and after amphetamine sensitization, Week 1, Week 5
Gray matter volume
Time frame: Before and after amphetamine sensitization, Week 1, Week 5
Functional connectivity
Time frame: Before and after amphetamine sensitization, Week 1, Week 5
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2018.
- Background: PubMed 27613293Weidenauer A, Bauer M, Sauerzopf U, Bartova L, Praschak-Rieder N, Sitte HH, Kasper S, Willeit M. Making Sense of: Sensitization in Schizophrenia. Int J Neuropsychopharmacol. 2016 Dec 31;20(1):1-10. doi: 10.1093/ijnp/pyw081. Print 2017 Jan.
- Background: PubMed 27690184Sauerzopf U, Sacco R, Novarino G, Niello M, Weidenauer A, Praschak-Rieder N, Sitte H, Willeit M. Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence. Eur J Neurosci. 2017 Jan;45(1):45-57. doi: 10.1111/ejn.13418. Epub 2016 Oct 19.
- Individual participant dataSharing planned: Undecided
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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.
Ana Weidenauer, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dextroamphetamine Sulfate in people with Schizophrenia and Psychosis, run by Medical University of Vienna at 1 site in Austria.
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 7 inclusion and 18 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: status not confirmed, as of the sponsor's last update on 19 Apr 2018. 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 Austria. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ana Weidenauer, MD (+43140400 ext. 38370, ana.weidenauer@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
[18F]FDOPA Ki values (time frame: Baseline and 2 weeks after amphetamine sensitization, Week 1 and Week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03223844, which also lists 2 linked publications.
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 19 Apr 2018.