HDAC Inhibitor Augmentation to Clozapine
| Status: | Withdrawn |
|---|---|
| Conditions: | Schizophrenia |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | 18 - 60 |
| Updated: | 2/24/2019 |
| Start Date: | April 2017 |
| End Date: | February 2019 |
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.
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.
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.
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.
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
We found this trial at
1
site
Virginia Commonwealth University Since our founding as a medical school in 1838, Virginia Commonwealth University...
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