HDAC Inhibitor Augmentation to Clozapine
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| ClinicalTrials.gov Identifier: NCT03263533 |
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Recruitment Status :
Withdrawn
(PIs were unable to recruit any participants)
First Posted : August 28, 2017
Last Update Posted : February 22, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Schizophrenia | Drug: Vorinostat Oral Capsule Group 1 Drug: Vorinostat Oral Capsule Group 2 | Early Phase 1 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 0 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Treatment |
| Official Title: | HDAC Inhibitor Augmentation to Clozapine |
| Estimated Study Start Date : | April 2017 |
| Estimated Primary Completion Date : | February 2019 |
| Estimated Study Completion Date : | February 2019 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Vorinostat Group 1 (P-V-P-P)
This group will receive this sequence after the 1 initial week washout: vorinstat (4 weeks) placebo (1 week) placebo (4 weeks) |
Drug: Vorinostat Oral Capsule Group 1
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. |
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Experimental: Vorinostat Group 2 (P-P-P-V)
This group will receive this sequence after the 1 initial week washout: placebo (4 weeks) placebo (1 week) vorinostat (4 weeks) |
Drug: Vorinostat Oral Capsule Group 2
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. |
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 60 Years (Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Diagnosed with DSM-5 Schizophrenia
- Receiving stable dose pf clozapine (≥ 300 mg per day) for at least 6 months before entering the study
Exclusion Criteria:
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03263533
| United States, Virginia | |
| Virginia Commonwealth University | |
| Richmond, Virginia, United States, 23298 | |
| Principal Investigator: | Javier Gonzalez-Maeso, PhD | Virginia Commonwealth University |
| Responsible Party: | Virginia Commonwealth University |
| ClinicalTrials.gov Identifier: | NCT03263533 |
| Other Study ID Numbers: |
HM20007977 |
| First Posted: | August 28, 2017 Key Record Dates |
| Last Update Posted: | February 22, 2019 |
| Last Verified: | February 2019 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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