SchizophreniaPhase 2/3NCT00894842
Study of a Neurocognition Enhancing Agent in Patients With Schizophrenia
A Phase 2/3 study testing Pregnenolone in people with Schizophrenia, run by National Research Foundation, Singapore at 1 site in Singapore.
Trial summary
The purpose of this study is to determine whether pregnenolone will demonstrate significant improvements in cognitive functioning and negative symptoms compared to patients receiving placebo. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Pregnenolone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteSingapore
- Study dates
- Jun 2009to Sep 2011
- Phase
- Phase 2/3
- 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 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male and female subjects aged 21 to 65 years inclusively at screening.
- Current diagnosis of Schizophrenia established by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for at least 1 year prior to screening.
- Subjects can be either inpatients or outpatients.
- Provision of written informed consent.
- Able to understand and comply with the requirements of the study, as judged by the investigator.
- Subjects have to be treated with a first generation and/or second generation antipsychotic for the previous 8 weeks or longer, with no change in dose in ≥ 4 weeks at screening.
- Women of childbearing potential (less than two years post-menopausal or not surgically sterile), must have a negative urine pregnancy test at screening - and must use a highly effective method of birth control for at least one month prior to screening such as barrier methods, implants, sexual abstinence or vasectomised partner.
Who cannot join
- Subjects with a DSM-IV diagnosis of alcohol or other substance dependence (other than nicotine) within the last month.
- Subjects with a history of significant head injury/trauma, with loss of consciousness (LOC) for more than 1 hour, recurring seizures resulting from the head injury, clear cognitive sequelae of the injury, or cognitive rehabilitation following the injury.
- Subjects with a history of clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorders (e.g., unstable angina, seizures, cerebrovascular accident, decompensate congestive heart failure, CNS infection, HIV seropositivity), which would pose a risk to the patient if they were to participate in the study or that might confound the results of the study.
- Active medical conditions that are minor or well-controlled are not exclusionary if they are not likely to affect risk to the patient or the study results.
- Patients with hormone-sensitive tumours (such as breast, uterine, or prostate cancer) will be excluded.
- Clinically significant abnormalities in physical examination, ECG, or laboratory assessments.
Show all 13Show fewer
- Pregnant women or sexually active women of child-bearing potential, who are either not surgically-sterile or not using appropriate methods of birth control (urine pregnancy test will be performed at baseline and week 10 of the study to exclude pregnancy).
- Women who are breast-feeding.
- ECT treatment within the last 3 months.
- Use of oral contraceptives or other hormonal supplementation such as oestrogen.
- Subjects who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others.
- Known allergy to study medication.
- Participation in another drug trial within 4 weeks of this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A 10-week, Randomized, Double-Blind, Placebo-Controlled Trial of a Neurocognition Enhancing Agent(Pregnenolone) in Patients With Schizophrenia.
The purpose of this study is to determine whether pregnenolone will demonstrate significant improvements in cognitive functioning and negative symptoms compared to patients receiving placebo.
Read the detailed description
Aims:
Schizophrenia is one of the most disabling disorders to afflict mankind. Despite the low lifetime prevalence of schizophrenia (1% world-wide), it has an enormous burden in both economic cost and human suffering. There is currently no cure for schizophrenia and its cause is not well understood. Patients with schizophrenia also suffer from negative symptoms (loss of drive, apathy, poverty of speech) and severe cognitive impairments especially with memory, attention, processing of information - the latter of which is most robustly correlated with their role functioning in the community. Addressing these impairments with effective interventions is thus critically important but at this present moment, there is no effective treatment. Recent emerging data from animal studies and a pilot study on small group of patients with schizophrenia suggest that neurosteroids such as pregnenolone may be relevant to schizophrenia pathophysiology and treatment of neurocognitive impairments. This study will be a 10-week randomised double-blind placebo-controlled trial of the efficacy and safety of pregnenolone. Our hypothesis is patients with schizophrenia randomized to pregnenolone will demonstrate significant improvements in cognitive functioning and negative symptoms compared to patients receiving placebo. The primary aims of the study are to demonstrate the efficacy of pregnenolone in comparison to placebo in patients with schizophrenia which are assessed by changes (from baseline) in the composite score of the MATRICS Consensus Cognitive Battery (MCCB), BACS and the Scale for Assessment of Negative Symptoms (SANS). Changes in functionality will be assessed by the University of California Performance Based Skills Assessment (UPSA). Safety will be assessed with laboratory tests, well established scales for side effects as well as with a side-effects checklist.
Objectives:
To demonstrate the efficacy of pregnenolone in comparison to placebo in patients with schizophrenia and with cognitive impairment from randomization (Week 2) to Week 10 by using MATRICS Consensus Cognitive Battery, BACS, Scale for Assessment of Negative Symptoms, Performance Based Skills Assessment - Brief Version and Clinical Global Impression -Improvement (CGI-I).Additional safety data on pregnenolone in patients with schizophrenia will be provided.
Methodology:
The proposed study is a single-site, randomized, double blind placebo-controlled comparison of adjunctive pregnenolone and placebo. A total sample will consist of 120 clinically stable inpatients and outpatients with DSM IV schizophrenia, with 60 subjects randomized to each group. A best estimate diagnostic approach will be utilized, in which information from the Structured Clinical Interview for DSM-IV will be supplemented by information from family informants, previous psychiatrists, and medical records to generate a diagnosis. There will be a 2 week, single-blind placebo lead-in evaluation phase, in which subjects will undergo baseline diagnostic and medical testing, including a physical examination, Electrocardiogram (ECG), Complete Blood Counts (CBC), complete metabolic panel, urine toxicology, and urinalysis. The study is designed to confirm the pilot study results (n=9 per group; total of 18 patients of 21 randomized who completed at least 4 weeks of treatment) in a larger clinical trial (n=60 per group, 120 patients total). Identical to our pilot study, patients will be seen for a total of 6 study visits (every two weeks). The placebo arm is essential as there are no standard therapies for cognitive defects as yet.
Potential Benefits:
While patients may not personally be helped by taking part in this study, their participation may lead to knowledge that will help better understand the illness. It may also lead to better treatment for cognitive deficits and negative symptoms in schizophrenia.
Potential Risks:
Obtaining blood can cause pain, bleeding, bruising, or swelling at the site of the needle prick. There is a risk that some questions on the questionnaires might upset the patients or cause psychological distress. There are no known severe risks that had been associated with taking pregnenolone.
- Conditions
- Schizophrenia
- Being tested
- Pregnenolone, Placebo
- Keywords
- Schizophrenia, Pregnenolone, Neurocognition
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PregnenoloneDrug
Pregnenolone 50 mg BID x 14 days, followed by Pregnenolone 300 mg per day for 14 days (200 mg qAM and 100 mg qPM), followed by Pregnenolone 500 mg per day for the remainder of the 8-week trial (300 mg qAM and 200 mg qPM)
PlaceboDrug
Placebo 50 mg BID x 14 days, followed by Placebo 300 mg per day for 14 days (200 mg qAM and 100 mg qPM), followed by Placebo 500 mg per day for the remainder of the 8-week trial (300 mg qAM and 200 mg qPM)
| Study group | Role | What they receive |
|---|---|---|
| Pregnenolone | Active comparator | Not described Receives: Drug: Pregnenolone |
| Sugar pill | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Improvement in composite score of the MATRICS Consensus Cognitive Battery (MCCB) and BACS.
Measured: 10 weeks
Improvement of negative symptoms as assessed by the Scale for Assessment of Negative Symptoms (SANS).
Measured: 10 weeks
Secondary outcomes (3)
To provide additional safety data on pregnenolone in patients with schizophrenia via reported serious and non serious adverse events.
Measured: 10 weeks
Improvement of functional outcome by the University of California Performance Based Skills Assessment (UPSA-B)at Week 2, 6 and 10.
Measured: 10 weeks
Efficacy outcome variables will be evaluated by the Clinical Global Impression -Improvement (CGI-I) score at week 2 to week 10.
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2009 (estimated)
- Study startJun 2009
- Primary completionSep 2011
- Study completionSep 2011
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
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Research Foundation, Singapore
- Sponsor type
- Other government
- Collaborators
- Duke University, National University of Singapore, Singapore Clinical Research Institute
- Responsible party
- Principal investigator, Chong Siow Ann, National Research Foundation, Singapore
- Investigators
- Siow Ann Chong, Principal investigator, Vice Chairman of Medical Board (Research)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00894842
- Sponsor's protocol ID
- TCR-NS-003
- Status last verified
- Oct 2011
- First submitted
- 6 May 2009
- Last updated
- 6 Oct 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 10-week, Randomized, Double-Blind, Placebo-Controlled Trial of a Neurocognition Enhancing Agent(Pregnenolone) in Patients With Schizophrenia.
- ClinicalTrials.gov ID
- NCT00894842
- Acronym / sponsor ID
- TCR-NS-003
- Conditions
- Schizophrenia
- Keywords
- Schizophrenia, Pregnenolone, Neurocognition
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- National Research Foundation, SingaporeOther government
- Collaborators
- Duke University, National University of Singapore, Singapore Clinical Research Institute
- Study start
- Jun 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 7 May 2009 (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 purpose of this study is to determine whether pregnenolone will demonstrate significant improvements in cognitive functioning and negative symptoms compared to patients receiving placebo.
Detailed description
Aims:
Schizophrenia is one of the most disabling disorders to afflict mankind. Despite the low lifetime prevalence of schizophrenia (1% world-wide), it has an enormous burden in both economic cost and human suffering. There is currently no cure for schizophrenia and its cause is not well understood. Patients with schizophrenia also suffer from negative symptoms (loss of drive, apathy, poverty of speech) and severe cognitive impairments especially with memory, attention, processing of information - the latter of which is most robustly correlated with their role functioning in the community. Addressing these impairments with effective interventions is thus critically important but at this present moment, there is no effective treatment. Recent emerging data from animal studies and a pilot study on small group of patients with schizophrenia suggest that neurosteroids such as pregnenolone may be relevant to schizophrenia pathophysiology and treatment of neurocognitive impairments. This study will be a 10-week randomised double-blind placebo-controlled trial of the efficacy and safety of pregnenolone. Our hypothesis is patients with schizophrenia randomized to pregnenolone will demonstrate significant improvements in cognitive functioning and negative symptoms compared to patients receiving placebo. The primary aims of the study are to demonstrate the efficacy of pregnenolone in comparison to placebo in patients with schizophrenia which are assessed by changes (from baseline) in the composite score of the MATRICS Consensus Cognitive Battery (MCCB), BACS and the Scale for Assessment of Negative Symptoms (SANS). Changes in functionality will be assessed by the University of California Performance Based Skills Assessment (UPSA). Safety will be assessed with laboratory tests, well established scales for side effects as well as with a side-effects checklist.
Objectives:
To demonstrate the efficacy of pregnenolone in comparison to placebo in patients with schizophrenia and with cognitive impairment from randomization (Week 2) to Week 10 by using MATRICS Consensus Cognitive Battery, BACS, Scale for Assessment of Negative Symptoms, Performance Based Skills Assessment - Brief Version and Clinical Global Impression -Improvement (CGI-I).Additional safety data on pregnenolone in patients with schizophrenia will be provided.
Methodology:
The proposed study is a single-site, randomized, double blind placebo-controlled comparison of adjunctive pregnenolone and placebo. A total sample will consist of 120 clinically stable inpatients and outpatients with DSM IV schizophrenia, with 60 subjects randomized to each group. A best estimate diagnostic approach will be utilized, in which information from the Structured Clinical Interview for DSM-IV will be supplemented by information from family informants, previous psychiatrists, and medical records to generate a diagnosis. There will be a 2 week, single-blind placebo lead-in evaluation phase, in which subjects will undergo baseline diagnostic and medical testing, including a physical examination, Electrocardiogram (ECG), Complete Blood Counts (CBC), complete metabolic panel, urine toxicology, and urinalysis. The study is designed to confirm the pilot study results (n=9 per group; total of 18 patients of 21 randomized who completed at least 4 weeks of treatment) in a larger clinical trial (n=60 per group, 120 patients total). Identical to our pilot study, patients will be seen for a total of 6 study visits (every two weeks). The placebo arm is essential as there are no standard therapies for cognitive defects as yet.
Potential Benefits:
While patients may not personally be helped by taking part in this study, their participation may lead to knowledge that will help better understand the illness. It may also lead to better treatment for cognitive deficits and negative symptoms in schizophrenia.
Potential Risks:
Obtaining blood can cause pain, bleeding, bruising, or swelling at the site of the needle prick. There is a risk that some questions on the questionnaires might upset the patients or cause psychological distress. There are no known severe risks that had been associated with taking pregnenolone.
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 |
|---|---|---|
| Pregnenolone | Active comparator | Drug: Pregnenolone |
| Sugar pill | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male and female subjects aged 21 to 65 years inclusively at screening.
- Current diagnosis of Schizophrenia established by Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria for at least 1 year prior to screening.
- Subjects can be either inpatients or outpatients.
- Provision of written informed consent.
- Able to understand and comply with the requirements of the study, as judged by the investigator.
Key exclusion criteria (13 listed)
- Subjects with a DSM-IV diagnosis of alcohol or other substance dependence (other than nicotine) within the last month.
- Subjects with a history of significant head injury/trauma, with loss of consciousness (LOC) for more than 1 hour, recurring seizures resulting from the head injury, clear cognitive sequelae of the injury, or cognitive rehabilitation following the injury.
- Subjects with a history of clinically significant neurological, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, and/or urological disorders (e.g., unstable angina, seizures, cerebrovascular accident, decompensate congestive heart failure, CNS infection, HIV seropositivity), which would pose a risk to the patient if they were to participate in the study or that might confound the results of the study.
- Clinically significant abnormalities in physical examination, ECG, or laboratory assessments.
- Pregnant women or sexually active women of child-bearing potential, who are either not surgically-sterile or not using appropriate methods of birth control (urine pregnancy test will be performed at baseline and week 10 of the study to exclude pregnancy).
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 |
|---|---|---|
| PregnenolonePregnenolone 50 mg BID x 14 days, followed by Pregnenolone 300 mg per day for 14 days (200 mg qAM and 100 mg qPM), followed by Pregnenolone 500 mg per day for the remainder of the 8-week trial (300 mg qAM and 200 mg qPM) | Drug | Pregnenolone |
| PlaceboPlacebo 50 mg BID x 14 days, followed by Placebo 300 mg per day for 14 days (200 mg qAM and 100 mg qPM), followed by Placebo 500 mg per day for the remainder of the 8-week trial (300 mg qAM and 200 mg qPM) | Drug | Sugar pill |
Primary outcome
Improvement in composite score of the MATRICS Consensus Cognitive Battery (MCCB) and BACS.
Time frame: 10 weeks
Improvement of negative symptoms as assessed by the Scale for Assessment of Negative Symptoms (SANS).
Time frame: 10 weeks
3 secondary outcomes
To provide additional safety data on pregnenolone in patients with schizophrenia via reported serious and non serious adverse events.
Time frame: 10 weeks
Improvement of functional outcome by the University of California Performance Based Skills Assessment (UPSA-B)at Week 2, 6 and 10.
Time frame: 10 weeks
Efficacy outcome variables will be evaluated by the Clinical Global Impression -Improvement (CGI-I) score at week 2 to week 10.
Time frame: 10 weeks
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 6 Oct 2011.
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
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.
Siow Ann Chong principal investigator
Vice Chairman of Medical Board (Research)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Pregnenolone in people with Schizophrenia, run by National Research Foundation, Singapore at 1 site in Singapore.
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 7 inclusion and 13 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 6 Oct 2011. 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 Singapore. 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Improvement in composite score of the MATRICS Consensus Cognitive Battery (MCCB) and BACS. (time frame: 10 weeks). 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 6 Oct 2011.