SchizophreniaEarly Phase 1NCT01519557
Pharmacologic and Clinical Testing of a D1 Agonist for Cognitive Enhancement in Neuropsychiatric Disorders
A Early Phase 1 study testing DAR-100A in people with Schizophrenia and Schizoaffective Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- DAR-100A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2011to Nov 2013
- Phase
- Early Phase 1
- 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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
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- Impaired intellectual functioning
- Orthostatic hypotension
- BP systolic BP <90 or > 140 or diastolic BP < 60 or > 90
- Antipsychotic polypharmacy within the previous four weeks.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
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.
Read the detailed description
Schizophrenia (SCZ) manifests as positive symptoms, negative symptoms and cognitive disturbances. To date, all of the available medications to treat schizophrenia bind primarily to the dopamine-2 (D2) receptor in the brain, and are only effective at treating the positive symptoms of schizophrenia. This is unfortunate given that negative and cognitive symptoms account for most of the disability in schizophrenia.
Emerging research over the past several decades has suggested a potential role for the dopamine-1 (D1) receptor in schizophrenia, as well as a role for D1 receptor stimulation in improving cognitive deficits. DAR-0100A is a new medication that binds selectively to the D1 receptor. It has been found to be safe when given to individuals with schizophrenia, and preliminary data suggests that it may be able to help with cognitive deficits.
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. Patients will 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
- Being tested
- DAR-100A, Placebo
- 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.
DAR-100ADrug
15mg or 0.5mg of DAR-100A intravenously over 30 minutes for 5 days, 9 days off then again for 5 more days
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| DAR-100A | Experimental | DAR-0100A is a dopamine D1 full agonist, the active component of the racemic mixture DAR-0100 Receives: Drug: DAR-100A |
| Placebo | Placebo comparator | Intravenously over 30 minutes for 5 days, 9 days off then again for 5 more days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Day 0 (baseline) and Day 5
Secondary outcomes (1)
Change from Baseline in cognitive performance after 5 days study drug administration.
The main outcome measures will be the change in composite score on the MATRICS Consensus Cognitive Battery (MCCB) and CogState Schizophrenia Test batteries from baseline(Day 0) and after repeated administration of DAR-0100A or placebo (Day 5). These batteries are also designed to be repeatable (insensitive to practice effects)and to allow for measurements of changes in performance (no floor or ceiling effects).
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2012 (estimated)
- Study startApr 2011
- Primary completionAug 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jeffrey A Lieberman, M.D., Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01519557
- Sponsor's protocol ID
- #6329
- Other IDs
- U01MH076544-03
- Status last verified
- Feb 2015
- First submitted
- 13 Jan 2012
- Last updated
- 4 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacologic and Clinical Testing of a D1 Agonist for Cognitive Enhancement in Neuropsychiatric Disorders
- ClinicalTrials.gov ID
- NCT01519557
- Acronym / sponsor ID
- #6329
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 27 Jan 2012 (estimated)
- 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.
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.
Detailed description
Schizophrenia (SCZ) manifests as positive symptoms, negative symptoms and cognitive disturbances. To date, all of the available medications to treat schizophrenia bind primarily to the dopamine-2 (D2) receptor in the brain, and are only effective at treating the positive symptoms of schizophrenia. This is unfortunate given that negative and cognitive symptoms account for most of the disability in schizophrenia.
Emerging research over the past several decades has suggested a potential role for the dopamine-1 (D1) receptor in schizophrenia, as well as a role for D1 receptor stimulation in improving cognitive deficits. DAR-0100A is a new medication that binds selectively to the D1 receptor. It has been found to be safe when given to individuals with schizophrenia, and preliminary data suggests that it may be able to help with cognitive deficits.
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. Patients will 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| DAR-100A | Experimental | Drug: DAR-100ADAR-0100A is a dopamine D1 full agonist, the active component of the racemic mixture DAR-0100 |
| Placebo | Placebo comparator | Drug: PlaceboIntravenously over 30 minutes for 5 days, 9 days off then again for 5 more days |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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)
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 |
|---|---|---|
| DAR-100A15mg or 0.5mg of DAR-100A intravenously over 30 minutes for 5 days, 9 days off then again for 5 more days | Drug | DAR-100A |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
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.
Time frame: Day 0 (baseline) and Day 5
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.
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.
Time frame: Day 0 (baseline) and Day 5
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.
1 secondary outcome
Change from Baseline in cognitive performance after 5 days study drug administration.
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2015.
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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.
Jeffrey A Lieberman, M.D. principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing DAR-100A in people with Schizophrenia and Schizoaffective Disorder, run by New York State Psychiatric Institute at 1 site in United States.
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 6 inclusion and 10 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: finished, as of the sponsor's last update on 4 Mar 2015. 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 United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Day 0 (baseline) and Day 5). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Mar 2015; AzTrials last refreshed its copy on 7 Nov 2026.