Paliperidone and Lithium in the Treatment of Suicidality - Treatment Indication and Epigenetic Regulation

NCT ID: NCT01134731

Last Updated: 2016-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-05-31
• Study Completion Date: 2014-02-28

Brief Summary

The study aims to use a combined clinical and translational approach to identify an efficient pharmacotherapy for the acute management of suicidality and the epigenetic regulation associated with the treatment.The primary objective is a clinical trial to compare the efficacy of paliperidone versus lithium and placebo as adjunctive therapy to the standard of care antidepressants in the acute management of suicidality in depressed subjects.

Specific Aims 1 and 2 are described in detail below. Analysis for Specific Aim 2 is still underway.

Detailed Description

Specific Aim 1: The atypical antipsychotic, paliperidone, when initiated simultaneously with an antidepressant, is superior to lithium plus antidepressant in the early intervention of suicidality in patients with Major Depressive Disorder (MDD). The goal of this aim is to examine the clinical efficacy of paliperidone in reducing suicidality, with a focus on early intervention. The hypothesis is based on our recently completed pilot study in which we found that the atypical antipsychotic, risperidone, had a rapid onset of action to reduce suicidality in patients with MDD. In view of a shortage in acute pharmacological management of suicidality, this study will provide an important new treatment option for the life threatening psychiatric condition.

Specific Aim 2: Both paliperidone and lithium regulate epigenetics by stabilizing DNA methylation, which is correlated with inhibition of glycogen synthase kinase-3 (GSK3) activity and improved clinical symptoms. This exploratory aim is developed based on the recent findings that DNA methylation is involved in regulation of mood, behavior, and cognition, and the enzyme of this epigenetic mechanism - DNA methyltransferase-1 (DNMT1) is regulated by the therapeutic target Glycogen synthase kinase 3 (GSK3). We will measure the expression of DNMTs and DNA methylation of global DNA, Brain-derived neurotrophic factor (BDNF), and Tropomyosin receptor kinase B (TrkB) in peripheral blood before and after study drug treatment, and analyze their correlation with GSK3 activity and clinical symptoms in response to treatment. Outcomes from this study will provide important new information in future development of more effective treatment options for suicidality targeting epigenetic regulation.

Conditions

Major Depressive Disorder; Suicidal Ideation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

paliperidone

dose escalation , levels 1-5 daily dosing ranged from 1-5mg

Group Type: EXPERIMENTAL

paliperidone

Intervention Type: DRUG

1-5 mg daily (QD)

lithium

dose escalation, level 1-5 daily dosing 300-1500mg

Group Type: ACTIVE_COMPARATOR

lithium

Intervention Type: DRUG

300-1500mg QD

placebo

1-5 placebo capsules

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

1-5 placebo capsules

Interventions

paliperidone

1-5 mg daily (QD)

Intervention Type: DRUG

lithium

300-1500mg QD

Intervention Type: DRUG

Placebo

1-5 placebo capsules

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Male and female subjects who are able to provide informed consent

2. 19-65 years of age

3. Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) diagnosis of MDD by MINI International Neuropsychiatric Interview (MINI) and confirmed by psychiatric interview

4. Currently experiencing a depressive episode with suicidality (defined as having current suicidal thoughts occurring at least 3 out of 7 days in a week).

5. Montgomery-Asberg Depression Rating Scale (MADRS) must include a total score > 25 and a suicidal sub-score > 4.

Exclusion Criteria

1. Depressed patients without suicidality, patients with severe psychotic features or with primary diagnoses of bipolar disorder (BD), schizophrenia, schizoaffective disorder, or generalized anxiety disorder (GAD), and subjects who have been taking lithium or an antipsychotic in the past 2 weeks

2. Those with uncontrolled medical illnesses. Participants must be on any new medications for at least 30 days to be considered medically stable.

3. For patients with panic disorder, post-traumatic stress disorder (PTSD), borderline personality disorder (BPD), etc. be sure that MDD is the primary diagnosis. When in doubt, decisions will be made on a case-by-case basis.

4. Pregnant women.

5. Allergic to paliperidone, to any other ingredient in paliperidone ER or paliperidone palmitate, or to risperidone.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American Foundation for Suicide Prevention

OTHER

Sponsor Role: collaborator

Ortho-McNeil Janssen Scientific Affairs, LLC

INDUSTRY

Sponsor Role: collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Dr. Richard Shelton

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Richard C Shelton, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of Alabama at Birmingham

Locations

UAB

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

F100329001

Identifier Type: -

Identifier Source: org_study_id