Pharmacologic and Clinical Testing of a D1 Agonist for Cognitive Enhancement in Neuropsychiatric Disorders

NCT01519557 | Completed Early Phase 1 DMC

• 2 other identifiers: #6329U01MH076544-03
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to recruit individuals with schizophrenia who are symptomatically stable and already taking medications to participate in this study. The investigators will recruit 90 individuals with schizophrenia and randomize them to low and high doses of DAR-0100A, as well as to placebo. The investigators will have them stay in the hospital for several weeks and receive up to 10 doses of DAR-0100A. The investigators will also test their cognition before and after receiving DAR-0100A to see if DAR-0100A is helpful and perform MRI scans before and after taking the medication to see which areas of the brain are activated when DAR-0100A is administered. These tests will be very important because they will help the investigators determine whether the D1 receptor is a good treatment target for schizophrenia and whether more research and resources should be devoted to finding medications that target this system. Patients with schizophrenia will be free of other medical, psychiatric and neurological disorders including alcohol and substance dependence, and will be able to understand the nature of the study and to provide informed consent.

Conditions

Schizophrenia; Schizoaffective Disorder

Outcome Measures

Primary Outcomes (2)

• Change from Baseline in resting blood flow and neural activity during working memory tasks in the dorsolateral prefrontal cortex (DLPFC)after 5 days study drug administration.

  The investigators will measure neural activity during working memory (WM) tasks using blood-oxygen-level-dependent (BOLD)contrast function magnetic resonance imaging (fMRI) and the n-back task and self-ordered object working memory task (SOWMT), prior to (day 0, baseline) and after receiving sub-acute (day 5) treatment with DAR-0100A (15mg or 0.5mg) or placebo.

  Day 0 (baseline) and Day 5

• Change from Baseline in resting blood flow and neural activity during working memory tasks in the dorsolateral prefrontal cortex (DLPFC)after 5 days study drug administration.

  The investigators will measure neural activity during working memory (WM) tasks using blood-oxygen-level-dependent (BOLD)contrast function magnetic resonance imaging(fMRI) and the n-back task and self-ordered object working memory task (SOWMT), prior to (day 0, baseline) and after receiving sub-acute (day 5) treatment with DAR-0100A (15mg or 0.5mg) or placebo.

  Day 0 (baseline) and Day 5

Secondary Outcomes (1)

• Change from Baseline in cognitive performance after 5 days study drug administration.

  Patients will be tested at baseline and after repeated administration of DAR-0100A or placebo, and 3 months after the cessation of treatment with the D1 agonist

Study Arms (2)

DAR-100A

EXPERIMENTAL

DAR-0100A is a dopamine D1 full agonist, the active component of the racemic mixture DAR-0100

Drug: DAR-100A

Placebo

PLACEBO COMPARATOR

Intravenously over 30 minutes for 5 days, 9 days off then again for 5 more days

Drug: Placebo

Interventions

DAR-100A DRUG

15mg or 0.5mg of DAR-100A intravenously over 30 minutes for 5 days, 9 days off then again for 5 more days

DAR-100A

Placebo DRUG

Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Males or females between 18 and 55 years old
• Fulfill Diagnostic and Statistical Manual, version 4 (DSM-IV) criteria schizophrenic illness, schizophreniform or schizoaffective disorder
• A negative urine toxicology
• Capacity to understand the study and to give written informed consent
• Must be on a stable dose of risperidone, aripiprazole, lurasidone, iloperidone, paliperidone, or haloperidol for at least 4 weeks if oral adn 2 cycles if depot. Absence of any antipsychotic medications other than risperidone, aripiprazole, or haloperidol for at least 4 weeks if oral or 2 cycles if depot prior to the study. Mood stabilizers, benzodiazepines and antidepressants are allowed as long as the drugs have not been changed for 4 weeks.
• Psychiatrically stable

You may not qualify if:

• Pregnancy or lactation, lack of effective birth control during the 15 days before the initial day of the study and for the duration of the drug trial
• Presence or positive history of severe medical or neurological illness, or any cardiovascular or liver disease
• Any current use of amphetamines, opiates, cocaine, sedative-hypnotics, cannabis, or other psychoactive drugs (other than nicotine)
• Metal implants or paramagnetic objects contained within the body which may interfere with MRI scan
• A history of substance dependence (other than nicotine or cannabis) or substance abuse within the previous 6 months (other than nicotine)
• Any current use of anticholinergic or anticoagulant medications. Any current use of any medications that can affect cognition or clotting other than occasional nonsteroidal antiinflammatory drug (NSAID)
• Impaired intellectual functioning
• Orthostatic hypotension
• BP systolic BP \<90 or \> 140 or diastolic BP \< 60 or \> 90
• Antipsychotic polypharmacy within the previous four weeks.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Jeffrey A Lieberman, M.D.

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2012
• First Posted: January 27, 2012
• Study Start: April 1, 2011
• Primary Completion: August 1, 2013
• Study Completion: November 1, 2013
• Last Updated: March 4, 2015

Record last verified: 2015-02

Locations

US (1)