Pilot Study of Pregnenolone Augmentation Targeting Cognitive Symptoms in Persistently Symptomatic Patients With Schizophrenia

A study testing Pregnenolone in people with Schizophrenia, run by Durham VA Medical Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

This is a pilot study of pregnenolone as an augmentation treatment for schizophrenia. The goal of this placebo-controlled study is to provide preliminary efficacy data for potential pregnenolone effects on cognitive symptoms and negative symptoms in patients with schizophrenia. Read more about this study

Who is it for?: Ages 18 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: 28 participants
Where: 1 siteUnited States
Study dates: Jun 2005to Apr 2008
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

18-65 years of age, any ethnic group, either sex
Diagnostic and Statistical Manual, 4th edition (DSM IV) diagnosis of schizophrenia or schizoaffective disorder
Ability to participate fully in the informed consent process, or have a legal guardian able to participate in the informed consent process.
Patient cohort enriched for moderate to severe cognitive symptoms (composite Brief Assessment of Cognition in Schizophrenia (BACS) score 0-3 SD below the mean).
No change in antipsychotic for 8 weeks or longer. No change in antipsychotic dose for 4 weeks or longer.
No change in anticholinergic, benzodiazepine, or mood stabilizer medications for 4 weeks or longer.
No anticipated need to alter any of the above medications (antipsychotics, anticholinergics, benzodiazepines, or mood stabilizers) for the 10-week duration of the study.

Who cannot join

Unstable medical illness or neurologic illness (seizures, cerebrovascular accident); history of prostate, breast, uterine, or ovarian cancer.
Use of oral contraceptives or other hormonal supplementation such as estrogen.
Other concomitant medications for medical conditions will be addressed on a case-by-case base to determine if exclusionary.
Active expression of suicidal or homicidal ideation.
Comorbid substance dependence (other than nicotine dependence), or presenting symptoms likely substance-induced, as judged by a study physician.
Female patients who are pregnant or breast-feeding.
Known allergy to study medication.
Drugs with a narrow therapeutic index (e.g. thioridazine, mesoridazine, ziprasidone, clozapine, etc) will be excluded as suggested by the Federal Drug Administration (FDA); patients taking these agents will not be eligible for this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

Durham VAMC
Durham, North Carolina, 27705

Other trials in United States

About this study

Read the detailed description

See brief summary

Conditions: Schizophrenia
Being tested: Pregnenolone, Placebo
Keywords: Schizophrenia, Pregnenolone, Cognition, Negative Symptoms
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 twice a day (BID) x 2 weeks, Pregnenolone 150 mg BID x 2 weeks, Pregnenolone 250 mg BID x 4 weeks
PlaceboDrug
Placebo (similar to active comparator) 50 mg BID x 2 weeks, Placebo (similar to active comparator) 150 mg BID x 2 weeks, Placebo (similar to active comparator) 250 mg BID x 4 weeks

Study groups in NCT00560937
Study group	Role	What they receive
1	Active comparator	Pregnenolone Receives: Drug: Pregnenolone
2	Placebo comparator	Placebo Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Score on the Scale for the Assessment of Negative Symptoms (SANS), p=0.048
The SANS assesses negative symptoms in schizophrenia. The SANS consists of 21 clinical interview questions assessing negative symptoms of schizophrenia. Each question is rated on a scale of 0 (no symptoms) to 7 (severe symptoms).
Measured: SANS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Mean Change of Z-scores on the Brief Assessment of Cognition in Schizophrenia (BACS)
The BACS includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed. Z-scores are calculated from composite scores. Higher z-scores are indicative of better cognitive performance, lower z-scores are indicative of lower cognitive performance. Range of z-scores anticipated to be between -3 and 3.
Measured: Change in composite BACS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)
The MATRICS is a battery for the assessment of cognitive symptoms in patients with schizophrenia. Composite T-scores are calculated (T-score ranges are -20 to +80, and are normed on gender and age). Higher scores are indicative of better cognitive performance, lower scores are indicative of poorer cognitive performance.
Measured: Change in composite MATRICS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)

Secondary outcomes (3)

Mean Score Change in Calgary Depression Scale for Schizophrenia (CDSS)
The CDSS is used measure to investigate depressive symptoms in schizophrenia. The measure includes 9 questions ranked from 0 (no symptoms) to 3 (severe symptoms). Range of possible scores: 0-27.
Measured: Change in CDSS scores at baseline and 8 weeks (at least 4 weeks; last observation carried forward)
Clinical Global Impression Scale (CGI-I)
The CGI-I is a commonly used psychiatric scale to assess overall general improvement. The CGI-I consists of one interviewer-rated question on a scale of 1-7. Lower scores are indicative of fewer symptoms; while higher scores are indicative of more symptoms.
Measured: CGI-I scores at 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Mean Score on the Positive and Negative Symptom Scale (PANSS)
The PANSS is a widely used measure with several subdomains, including positive symptoms, negative symptoms, and general psychopathology of schizophrenia. Lower scores are indicative of fewer symptoms; higher scores are indicative of more symptoms. Total PANSS scores range from 0-20.
Measured: Change in PANSS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2005Apr 2008

First posted20 Nov 2007 (estimated)
Study startJun 2005
Primary completionApr 2006
Study completionApr 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 28 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00560937
Sponsor's protocol ID: VA IRB# 00924
Status last verified: Aug 2015
First submitted: 19 Nov 2007
Last updated: 25 Aug 2015
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Aug 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot Study of Pregnenolone Augmentation Targeting Cognitive Symptoms in Persistently Symptomatic Patients With Schizophrenia
ClinicalTrials.gov ID: NCT00560937
Acronym / sponsor ID: VA IRB# 00924
Conditions: Schizophrenia
Keywords: Schizophrenia, Pregnenolone, Cognition, Negative Symptoms
Study type: Interventional
Recruitment status: Completed
Enrolment: 28 participants (actual)
Lead sponsor: Durham VA Medical CenterUS federal agency
Study start: Jun 2005
Primary completion: Apr 2006 (actual)
Study completion: Apr 2008 (actual)
First posted: 20 Nov 2007 (estimated)
Results: Posted 28 Dec 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

See brief summary

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
1	Active comparator	Drug: PregnenolonePregnenolone
2	Placebo comparator	Drug: PlaceboPlacebo

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

18-65 years of age, any ethnic group, either sex
Diagnostic and Statistical Manual, 4th edition (DSM IV) diagnosis of schizophrenia or schizoaffective disorder
Ability to participate fully in the informed consent process, or have a legal guardian able to participate in the informed consent process.
Patient cohort enriched for moderate to severe cognitive symptoms (composite Brief Assessment of Cognition in Schizophrenia (BACS) score 0-3 SD below the mean).
No change in antipsychotic for 8 weeks or longer. No change in antipsychotic dose for 4 weeks or longer.

Key exclusion criteria (8 listed)

Unstable medical illness or neurologic illness (seizures, cerebrovascular accident); history of prostate, breast, uterine, or ovarian cancer.
Use of oral contraceptives or other hormonal supplementation such as estrogen.
Other concomitant medications for medical conditions will be addressed on a case-by-case base to determine if exclusionary.
Active expression of suicidal or homicidal ideation.
Comorbid substance dependence (other than nicotine dependence), or presenting symptoms likely substance-induced, as judged by a study physician.

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 twice a day (BID) x 2 weeks, Pregnenolone 150 mg BID x 2 weeks, Pregnenolone 250 mg BID x 4 weeks	Drug	1
PlaceboPlacebo (similar to active comparator) 50 mg BID x 2 weeks, Placebo (similar to active comparator) 150 mg BID x 2 weeks, Placebo (similar to active comparator) 250 mg BID x 4 weeks	Drug	2

Primary outcome

Mean Score on the Scale for the Assessment of Negative Symptoms (SANS), p=0.048
Time frame: SANS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
The SANS assesses negative symptoms in schizophrenia. The SANS consists of 21 clinical interview questions assessing negative symptoms of schizophrenia. Each question is rated on a scale of 0 (no symptoms) to 7 (severe symptoms).
Mean Change of Z-scores on the Brief Assessment of Cognition in Schizophrenia (BACS)
Time frame: Change in composite BACS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
The BACS includes brief assessments of executive functions, verbal fluency, attention, verbal memory, working memory and motor speed. Z-scores are calculated from composite scores. Higher z-scores are indicative of better cognitive performance, lower z-scores are indicative of lower cognitive performance. Range of z-scores anticipated to be between -3 and 3.
Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)
Time frame: Change in composite MATRICS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
The MATRICS is a battery for the assessment of cognitive symptoms in patients with schizophrenia. Composite T-scores are calculated (T-score ranges are -20 to +80, and are normed on gender and age). Higher scores are indicative of better cognitive performance, lower scores are indicative of poorer cognitive performance.

3 secondary outcomes

Mean Score Change in Calgary Depression Scale for Schizophrenia (CDSS)
Time frame: Change in CDSS scores at baseline and 8 weeks (at least 4 weeks; last observation carried forward)
Clinical Global Impression Scale (CGI-I)
Time frame: CGI-I scores at 8 weeks post-randomization (at least 4 weeks; last observation carried forward)
Mean Score on the Positive and Negative Symptom Scale (PANSS)
Time frame: Change in PANSS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)

Results and safety

Results posted to the registry on 28 Dec 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pregnenolone	10	9
Placebo	11	9

Primary outcome: Mean Score on the Scale for the Assessment of Negative Symptoms (SANS), p=0.048

Time frame: SANS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward). Mean (Standard Deviation). Unit: units on a scale

Measure	Pregnenolone n = 8	Placebo n = 9
Value	-10.38 (10.18)	-2.33 (4.42)

Pregnenolone vs Placebo: p = .048, t-test, 2 sided

Population analysed: Pilot proof of concept study

Primary outcome: Mean Change of Z-scores on the Brief Assessment of Cognition in Schizophrenia (BACS)

Time frame: Change in composite BACS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward). Mean (Standard Deviation). Unit: units on a scale

Measure	Pregnenolone n = 9	Placebo n = 9
Value	0.60 (0.78)	0.22 (0.47)

Placebo: p = 0.22, t-test, 2 sided

Primary outcome: Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)

Time frame: Change in composite MATRICS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward). Mean (Standard Deviation). Unit: units on a scale

Measure	Pregnenolone n = 9	Placebo n = 9
Value	7.00 (8.87)	7.00 (4.95)

Pregnenolone vs Placebo: p = 1.0, t-test, 2 sided

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were recorded during each study visit (study visits occurred every two weeks, a total of 5 study visits) for the duration of the 10 week study (following a 2 week placebo lead-in).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pregnenolone	0 of 9 (0%)	4 of 9 (44.4%)	Not reported
Placebo	0 of 9 (0%)	5 of 9 (55.6%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Christine E Marx, MD, MA principal investigator

Durham VAMC

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Pregnenolone in people with Schizophrenia, run by Durham VA Medical Center 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 7 inclusion and 8 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 25 Aug 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Mean Score on the Scale for the Assessment of Negative Symptoms (SANS), p=0.048 (time frame: SANS scores at baseline and 8 weeks post-randomization (at least 4 weeks; last observation carried forward)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00560937.

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 25 Aug 2015.