Influence of Amphetamine-induced Sensitization on Dopamine Synthesis and Release

NCT03223844 | Unknown

• 1 other identifier: 16969
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief 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 amphetamine sensitization in order to better understand adaptive mechanisms of the dopamine system.

Conditions

Schizophrenia; Psychosis; Sensitisation

Keywords

Dopamine; Amphetamine; Positron Emission Tomography; Magnetic Resonance Imaging; Schizophrenia; Psychosis; [18F]FDOPA; [11C]-(+)-PHNO

Outcome Measures

Primary Outcomes (1)

• [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 Outcomes (11)

• [11C]-(+)-PHNO BPND values

  Baseline and 2 weeks after amphetamine sensitization, Week 1 and Week 4

• Subjective ratings of amphetamine effects (Drug Effects Questionnaire)

  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)

  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

  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

  Baseline, Week 1

Study Arms (1)

Healthy subjects

EXPERIMENTAL

Measurement of Dextroamphetamine Sulfate-induced dopamine release and synthesis before and after amphetamine sensitization.

Drug: Dextroamphetamine Sulfate

Interventions

Dextroamphetamine Sulfate DRUG

Repeated oral administration of dexamphetamine 0.4mg/KG bodyweight four times.

Also known as: [11C]-(+)-PHNO PET, [18F]FDOPA PET

Healthy subjects

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

Related Publications (2)

• 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.

  PMID: 27613293 BACKGROUND

• 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.

  PMID: 27690184 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Interventions

Dextroamphetamine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amphetamine; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Study Officials

• Ana Weidenauer, MD

  Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ana Weidenauer, MD

CONTACT

+43140400; ana.weidenauer@meduniwien.ac.at

Matthaeus Willeit, MD

CONTACT

+43140400; matthaeus.willeit@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 8, 2017
• First Posted: July 21, 2017
• Study Start: January 1, 2018
• Primary Completion: August 1, 2021
• Study Completion: December 1, 2021
• Last Updated: April 19, 2018

Record last verified: 2018-04

Locations

AU (1)