SchizophreniaEarly Phase 1NCT03263533
HDAC Inhibitor Augmentation to Clozapine
A Early Phase 1 study testing Vorinostat Oral Capsule Group 1 and Vorinostat Oral Capsule Group 2 in people with Schizophrenia, run by Virginia Commonwealth University.
Trial summary
The main goal of this pilot study is to test the extent to which adjunctive treatment with the histone deacetylase (HDAC) inhibitor vorinostat improves brain plasticity and cognition in a pilot placebo-controlled trial in patients with schizophrenia who are on clozapine. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Vorinostat Oral Capsule Group 1 and Vorinostat Oral Capsule Group 2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Apr 2017to Feb 2019
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Diagnosed with DSM-5 Schizophrenia
- Receiving stable dose pf clozapine (≥ 300 mg per day) for at least 6 months before entering the study
Who cannot join
- Taking specific psychotropic medications (lamotrigine and valproic acid)
- Current or recent (12-months) substance use or induced disorder
- History of significant neurological or medical disorders
- Intellectual disability
- Known contraindications to the administration of vorinostat per product labeling
- Women currently pregnant, planning to become pregnant, or receiving hormone therapy and refusing any form of birth control
About this study
The main goal of this pilot study is to test the extent to which adjunctive treatment with the histone deacetylase (HDAC) inhibitor vorinostat improves brain plasticity and cognition in a pilot placebo-controlled trial in patients with schizophrenia who are on clozapine.
Read the detailed description
The goal of this study is to perform a pilot clinical study with a small sample of subjects to evaluate the safety and tolerability of vorinostat when combined with clozapine treatment in patients with schizophrenia. The investigators will also evaluate the potential translation of our preclinical data into a clinical use of vorinostat for cognitive impairment in clozapine-treated schizophrenic patients.
Potential participants will be receiving stables doses of clozapine for a minimum period of 6 months before entry into the study. Clozapine was selected because i) the majority of our studies in mouse models were performed after chronic treatment with this atypical antipsychotic, and ii) the investigators' data in postmortem human brain samples of subjects with antemortem diagnosis of schizophrenia suggest up-regulation of HDAC2 in frontal cortex of schizophrenic subjects treated with atypical, but not typical, antipsychotic drugs.
The HDAC inhibitor vorinostat was selected because preliminary data suggest that chronic treatment with vorinostat improves HDAC2-dependent cognitive function in rodent models. Additionally, vorinostat is the first HDAC inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of cutaneous T-cell lymphoma. Dose(s) of vorinostat have been selected based on previous clinical studies in such patients with brain metastasis.
- Conditions
- Schizophrenia
- Being tested
- Vorinostat Oral Capsule Group 1, Vorinostat Oral Capsule Group 2
- Keywords
- schizophrenia, clozapine, vorinostat, HDAC, histone deacetylase inhibitor
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vorinostat Oral Capsule Group 1Drug
Following the initial washout and first 4-week period of the trial, all patients will enter a second 1-week washout. After the washout, all patients will then enter a second 4 week alternate treatment (vorinostat or placebo). During the vorinostat sequence, doses will be increased over the first 2 weeks in each phase of the crossover study, starting by 100 mg per day, and increasing to 200 mg by week 2 and 300 mg per day at the start of week 3 until the end of week 4.
Vorinostat Oral Capsule Group 2Drug
Following the initial washout and first 4-week period of the trial, all patients will enter a second 1-week washout. After the washout, all patients will then enter a second 4 week alternate treatment (vorinostat or placebo). During the vorinostat sequence, doses will be increased over the first 2 weeks in each phase of the crossover study, starting by 100 mg per day, and increasing to 200 mg by week 2 and 300 mg per day at the start of week 3 until the end of week 4.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat Group 1 (P-V-P-P) | Experimental | This group will receive this sequence after the 1 initial week washout:
vorinstat (4 weeks) placebo (1 week) placebo (4 weeks) Receives: Drug: Vorinostat Oral Capsule Group 1 |
| Vorinostat Group 2 (P-P-P-V) | Experimental | This group will receive this sequence after the 1 initial week washout:
placebo (4 weeks) placebo (1 week) vorinostat (4 weeks) Receives: Drug: Vorinostat Oral Capsule Group 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Safety of vorinostat measured by number of adverse events
Measured: 10 weeks
Change in clinical cognitive symptoms during adjunctive vorinostat therapy in schizophrenia patients treated with clozapine
Participants will be given a cognitive test to assess executive function and speed.
Measured: Baseline, Visit 4 (end of first intervention group/week 4), Visit 7 (end of study/10 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2017
- Study startApr 2017 (estimated)
- Primary completionFeb 2019 (estimated)
- Study completionFeb 2019 (estimated)
Why it stopped: PIs were unable to recruit any participants
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.
- More trials run by Virginia Commonwealth UniversityThe sponsor's other registered studies.
- 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
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Virginia Commonwealth University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Javier Gonzalez-Maeso, PhD, Principal investigator, Virginia Commonwealth University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03263533
- Sponsor's protocol ID
- HM20007977
- Status last verified
- Oct 2024
- First submitted
- 14 Aug 2017
- Last updated
- 15 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HDAC Inhibitor Augmentation to Clozapine
- ClinicalTrials.gov ID
- NCT03263533
- Acronym / sponsor ID
- HM20007977
- Conditions
- Schizophrenia
- Keywords
- schizophrenia, clozapine, vorinostat, HDAC, histone deacetylase inhibitor
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PIs were unable to recruit any participants
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Virginia Commonwealth UniversityUniversity, hospital or other
- Study start
- Apr 2017 (estimated)
- Primary completion
- Feb 2019 (estimated)
- Study completion
- Feb 2019 (estimated)
- First posted
- 28 Aug 2017 (actual)
- 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 main goal of this pilot study is to test the extent to which adjunctive treatment with the histone deacetylase (HDAC) inhibitor vorinostat improves brain plasticity and cognition in a pilot placebo-controlled trial in patients with schizophrenia who are on clozapine.
Detailed description
The goal of this study is to perform a pilot clinical study with a small sample of subjects to evaluate the safety and tolerability of vorinostat when combined with clozapine treatment in patients with schizophrenia. The investigators will also evaluate the potential translation of our preclinical data into a clinical use of vorinostat for cognitive impairment in clozapine-treated schizophrenic patients.
Potential participants will be receiving stables doses of clozapine for a minimum period of 6 months before entry into the study. Clozapine was selected because i) the majority of our studies in mouse models were performed after chronic treatment with this atypical antipsychotic, and ii) the investigators' data in postmortem human brain samples of subjects with antemortem diagnosis of schizophrenia suggest up-regulation of HDAC2 in frontal cortex of schizophrenic subjects treated with atypical, but not typical, antipsychotic drugs.
The HDAC inhibitor vorinostat was selected because preliminary data suggest that chronic treatment with vorinostat improves HDAC2-dependent cognitive function in rodent models. Additionally, vorinostat is the first HDAC inhibitor approved by the U.S. Food and Drug Administration (FDA) for the treatment of cutaneous T-cell lymphoma. Dose(s) of vorinostat have been selected based on previous clinical studies in such patients with brain metastasis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vorinostat Group 1 (P-V-P-P) | Experimental | Drug: Vorinostat Oral Capsule Group 1This group will receive this sequence after the 1 initial week washout: vorinstat (4 weeks) placebo (1 week) placebo (4 weeks) |
| Vorinostat Group 2 (P-P-P-V) | Experimental | Drug: Vorinostat Oral Capsule Group 2This group will receive this sequence after the 1 initial week washout: placebo (4 weeks) placebo (1 week) vorinostat (4 weeks) |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Diagnosed with DSM-5 Schizophrenia
- Receiving stable dose pf clozapine (≥ 300 mg per day) for at least 6 months before entering the study
Key exclusion criteria (6 listed)
- Taking specific psychotropic medications (lamotrigine and valproic acid)
- Current or recent (12-months) substance use or induced disorder
- History of significant neurological or medical disorders
- Intellectual disability
- Known contraindications to the administration of vorinostat per product labeling
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 |
|---|---|---|
| Vorinostat Oral Capsule Group 1Following the initial washout and first 4-week period of the trial, all patients will enter a second 1-week washout. After the washout, all patients will then enter a second 4 week alternate treatment (vorinostat or placebo). During the vorinostat sequence, doses will be increased over the first 2 weeks in each phase of the crossover study, starting by 100 mg per day, and increasing to 200 mg by week 2 and 300 mg per day at the start of week 3 until the end of week 4. | Drug | Vorinostat Group 1 (P-V-P-P) |
| Vorinostat Oral Capsule Group 2Following the initial washout and first 4-week period of the trial, all patients will enter a second 1-week washout. After the washout, all patients will then enter a second 4 week alternate treatment (vorinostat or placebo). During the vorinostat sequence, doses will be increased over the first 2 weeks in each phase of the crossover study, starting by 100 mg per day, and increasing to 200 mg by week 2 and 300 mg per day at the start of week 3 until the end of week 4. | Drug | Vorinostat Group 2 (P-P-P-V) |
Primary outcome
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: 10 weeks
Safety of vorinostat measured by number of adverse events
Change in clinical cognitive symptoms during adjunctive vorinostat therapy in schizophrenia patients treated with clozapine
Time frame: Baseline, Visit 4 (end of first intervention group/week 4), Visit 7 (end of study/10 weeks)
Participants will be given a cognitive test to assess executive function and speed.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- Individual participant dataSharing planned: No
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of KarXT in Acutely Psychotic Japanese Adult Participants With Schizophrenia
Schizophrenia
Active, not recruitingPhase 2/3
Low Amplitude Pulse Seizure Therapy Versus Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy
Suicidal Ideation, Major Depressive Disorder
RecruitingObservational study
Effectiveness and Adverse-effect Switch Evaluation of Xanomeline and Trospium Chloride (KarXT)
Schizophrenia
Not yet recruitingPhase 1
A Study to Assess the Safety, Tolerability and Pharmacokinetics of XEP527 in Patients With Stable Schizophrenia
Schizophrenia
Not yet recruitingPhase 1
Phase I Trial of HHK101 in Patients With Schizophrenia
Schizophrenia
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.
Javier Gonzalez-Maeso, PhD principal investigator
Virginia Commonwealth University
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Vorinostat Oral Capsule Group 1 and Vorinostat Oral Capsule Group 2 in people with Schizophrenia, run by Virginia Commonwealth University.
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 2 inclusion and 6 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: withdrawn, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 was withdrawn before enrolling participants, so there are no results.
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?
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) (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 15 Oct 2024.