HDAC Inhibitor Augmentation to Clozapine

NCT03263533 | Withdrawn Early Phase 1 DMC FDA Drug

• 1 other identifier: HM20007977
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Schizophrenia

Keywords

schizophrenia; clozapine; vorinostat; HDAC; histone deacetylase inhibitor

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

  Safety of vorinostat measured by number of adverse events

  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.

  Baseline, Visit 4 (end of first intervention group/week 4), Visit 7 (end of study/10 weeks)

Study Arms (2)

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)

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)

Drug: Vorinostat Oral Capsule Group 2

Interventions

Vorinostat Oral Capsule Group 1 DRUG

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 Group 1 (P-V-P-P)

Vorinostat Oral Capsule Group 2 DRUG

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 Group 2 (P-P-P-V)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosed with DSM-5 Schizophrenia
• Receiving stable dose pf clozapine (≥ 300 mg per day) for at least 6 months before entering the study

You may not qualify if:

• 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

Sponsors & Collaborators

• Virginia Commonwealth University: lead

MeSH Terms

Conditions

Schizophrenia

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Javier Gonzalez-Maeso, PhD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2017
• First Posted: August 28, 2017
• Study Start: April 1, 2017
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: October 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share