Schizophrenia Clinical Trial
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.
Status | Recruiting |
Enrollment | 22 |
Est. completion date | December 2021 |
Est. primary completion date | August 2021 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 65 Years |
Eligibility |
Inclusion Criteria: - 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 Exclusion Criteria: - 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 - 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 |
Country | Name | City | State |
---|---|---|---|
Austria | Medical University of Vienna | Vienna |
Lead Sponsor | Collaborator |
---|---|
Medical University of Vienna |
Austria,
Sauerzopf 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. Review. — View Citation
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. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | [18F]FDOPA Ki values | Relative change in regional [18F]FDOPA Ki values after AMPH sensitization | Baseline and 2 weeks after amphetamine sensitization, Week 1 and Week 4 | |
Secondary | [11C]-(+)-PHNO BPND values | Relative change in regional [11C]-(+)-PHNO BPND values after AMPH administration before and after sensitization | Baseline and 2 weeks after amphetamine sensitization, Week 1 and Week 4 | |
Secondary | Subjective ratings of amphetamine effects (Drug Effects Questionnaire) | Subjective ratings will be assessed via questionnaire (Drug Effects Questionnaire) four times throughout the study. | 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 | |
Secondary | Subjective ratings of amphetamine effects (Subjective States Questionnaire) | Subjective ratings will be assessed via questionnaire (Subjective States Questionnaire) four times throughout the study. | 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 | |
Secondary | Cognitive measures | Working memory, reward processing and impulsivity will be assessed via a computerized test battery four times throughout the study | 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 | |
Secondary | Impulsiveness | The personality traits impulsiveness will be assessed once during study participation by the questionnaire Barrat Impulsiveness Scale (BIS). | Baseline, Week 1 | |
Secondary | Personality-related markers | Personality traits like novelty seeking will be assessed once during study participation using the Temperament and Character Inventory (TCI). | Baseline, Week 1 | |
Secondary | 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. | Baseline FDOPA scan, baseline PHNO + amphetamine scan, post-sensitization PHNO+ amphetamine scan, post-sensitization FDOPA scan, Time points: Week 1 Week 2 Week 4 | |
Secondary | Salivary cortisol | Salivary cortisol will be assessed using Salivettes ®. | 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. | |
Secondary | Fractional anisotropy (diffusion-weighted tensor imaging) of white matter | Fractional anisotropy of white matter will be measured by means of magnet resonance imaging. | Before and after amphetamine sensitization, Week 1, Week 5 | |
Secondary | Gray matter volume | Gray matter volume will be measured by means of magnet resonance imaging. T1 and PD sequences will be recorded. | Before and after amphetamine sensitization, Week 1, Week 5 | |
Secondary | Functional connectivity | Functional connectivity between brain regions will be measured by means of magnet resonance imaging during a resting state of the subject. | Before and after amphetamine sensitization, Week 1, Week 5 |
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