Imaging Dopamine D2 Agonist Binding Sites in Schizophrenia

NCT03999190 | Withdrawn

• 1 other identifier: 18-01207
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The goals of this study is to determine (1) if differences in D2/3 receptor affinity states exist between medication-free subjects with SCH (MF-S) compared with healthy controls (HC), (2) the degree to which pre- and post-synaptic factors contribute to increased striatal dopamine (DA) signaling in MF-S and (3) to test the hypotheses that optimal DA transmission in the dorsal caudate (DCA) is necessary for normal working memory (WM) function.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (2)

• base line Binding Potential (BPND)

  PET outcome measure of the density of "available" neuroreceptors and the affinity of a drug to that neuroreceptor.

  37 Days

• percent change in BPND

  Difference between BPND measured in the post-amphetamine condition (BPND AMPH) and BPND measured in the baseline condition (BPND BASE) expressed as a percentage of BPND BASE: BPND = 100 \* (BPND AMPH - BPND BASE)/BPND BASE.

  37 Days

Study Arms (2)

30 subjects with schizophrenia

Drug: NPA radiotracer; Drug: Raclopride radiotracer; Drug: Dextroamphetamine

30 healthy controls

Drug: NPA radiotracer; Drug: Raclopride radiotracer; Drug: Dextroamphetamine

Interventions

NPA radiotracer DRUG

\[11C\]NPA radiotracer, 2 injection per subject Antagonist (\[11C\]raclopride) and agonist (\[11C\]NPA) radiotracer will be used sequentially to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 medication free subjects with schizophrenia (MF-S) and 30 healthy control subjects (HC).

30 healthy controls; 30 subjects with schizophrenia

Raclopride radiotracer DRUG

\[11C\]raclopride radiotracer, 2 injections per subject Antagonist (\[11C\]raclopride) and agonist (\[11C\]NPA) radiotracer will be used sequentially to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 medication free subjects with schizophrenia (MF-S) and 30 healthy control subjects (HC).

30 healthy controls; 30 subjects with schizophrenia

Dextroamphetamine DRUG

Dextroamphetamine, one oral administration of 0.5 mg/kg per subject Antagonist (\[11C\]raclopride) and agonist (\[11C\]NPA) radiotracer will be used sequentially to measure binding potential (BPND) under baseline conditions and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 medication free subjects with schizophrenia (MF-S) and 30 healthy control subjects (HC).

30 healthy controls; 30 subjects with schizophrenia

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

SCHIZOPHRENIA patiens 18-35; Healthy Controls 18-35

You may qualify if:

• HEALTHY CONTROLS
• Males or females between 18 and 35 years old (History)
• Absence of current (i.e. last six months) psychiatric conditions (including alcohol and drug abuse). Subjects with a history of a non-psychotic psychiatric disorder who have been asymptomatic and not taking medication for the past 6 months may be eligible.
• (History, SCID-NP (non-patient version))
• A negative urine toxicology with the exception of cannabis; in the case of a positive urine cannabis test a salivary cannabis test will be administered on the day of the PET scans to ensure subjects have not used within 24 - 48 hours.
• (Urine toxicology)
• Medically Healthy (History, EKG, physical, labs (detailed labs are listed under screening procedures))
• Weight between 44 and 115 kg (physical exam)
• Baseline systolic BP of \< 150 and \> 100, diastolic BP \< 90 and \>60 and baseline HR less than 90 (Physical exam)
• SUBJECTS WITH SCHIZOPHRENIA Criteria (Assessment)
• Males or females between 18 and 35 years old (History)
• Fulfill DSM-V criteria for schizophrenic illness, schizophreniform or schizoaffective disorder (History, SCID)
• A negative urine toxicology with the exception of cannabis; in the case of a positive urine cannabis test a salivary cannabis test will be administered on the day of the PET scans to ensure subjects have not used within 24 - 48 hours.
• (Urine toxicology)
• Medically Healthy (History, EKG, physical, labs (detailed labs are listed in screening procedures))

You may not qualify if:

• HEALTHY CONTROLS
• Pregnancy or lactation, lack of effective birth control during 15 days before the scans\* (Blood or Urine pregnancy test, history)
• Presence or positive history of serious medical or neurological illness, including low hemoglobin and seizure history.
• (Medical and neurological history, EKG, blood tests)
• Any current use (within past month) of amphetamines, opiates, cocaine, sedative-hypnotics, ecstasy PCP.
• (History, urine toxicology)
• Any use of cannabis beyond occasional use (i.e. more than 2 - 4 times per month) (History, saliva cannabis test)
• Metal implants or paramagnetic objects contained within the body which may interfere with the MRI scan (but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant. Dental fillings do not present a risk for MRI), as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects" Shellock, PhD, Lippincott Williams and Wilkins, NY 2001. If there is any doubt, subjects will be excluded.
• (Interview and history)
• Lifetime exposure to radiation in the workplace; or participation in research protocols involving exposure to radiation within the previous year such that the total cumulative annual radiation dose (i.e., from participation in the previous research studies and this study) would exceed the radiation dose limits specified in the FDA regulations at 21 CFR 361.1, Radioactive Drugs Considered Generally Safe and Effective (i.e. annual cumulative radiation dose limit = 5 rems to gonads, blood-forming organs, lens of eye, whole body; 15 rems to other organs).
• (Interview and history)
• Medical history of chronic obstructive pulmonary disease or other chronic respiratory disorders (Medical history)
• More than one risk factor for coronary artery disease (smoking, cholesterol \> 240 mg/dl, sedentary lifestyle) baseline SBP \> 140 of DBP\> 90) (History, physical examination and blood chemistry)
• Positive Allen Test indicating lack of collateral flow to hand (Physical Exam)
• Subjects with family history of a psychotic disorder, drug and alcohol Abuse/Dependence in first-degree relatives. (History)

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Schizophrenia

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

• William Frankle

  New York Langone Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2019
• First Posted: June 26, 2019
• Study Start: July 1, 2019
• Primary Completion: July 1, 2025
• Study Completion: July 1, 2025
• Last Updated: May 29, 2020

Record last verified: 2020-05

Locations

US (1)