Paliperidone and Lithium in the Treatment of Suicidality - Treatment Indication and Epigenetic Regulation (AFSP)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT01134731|
Recruitment Status : Completed
First Posted : June 2, 2010
Results First Posted : January 29, 2016
Last Update Posted : March 3, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|Major Depressive Disorder Suicidal Ideation||Drug: paliperidone Drug: lithium Drug: Placebo||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||54 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Triple (Participant, Investigator, Outcomes Assessor)|
|Official Title:||Paliperidone and Lithium in the Treatment of Suicidality - Treatment Indication and Epigenetic Regulation|
|Study Start Date :||May 2010|
|Primary Completion Date :||February 2014|
|Study Completion Date :||February 2014|
dose escalation , levels 1-5 daily dosing ranged from 1-5mg
1-5 mg daily (QD)
Active Comparator: lithium
dose escalation, level 1-5 daily dosing 300-1500mg
Placebo Comparator: placebo
1-5 placebo capsules
1-5 placebo capsules
- Mean Score of Beck Scale for Suicidal Ideation of Three Treatment Groups (Paliperidone, Lithium and Placebo) After 3 Months of Treatment [ Time Frame: baseline to 12 weeks ]The Beck Scale for Suicidal Ideation will be used to measure the efficacy of the study drugs. The primary outcome measure is the Beck Suicide Scale Self Report. The primary outcome measure is the Beck Suicide Scale Self Report. It has 21 questions (subscales) with values ranging from 0-2. Therefore the total score ranges from 0-42, with lower scores indicating better outcomes. The subscales were summed to achieve a total score.
- Mean Score of Montgomery-Asberg Depression Scale of Three Treatment Groups (Paliperidone, Lithium and Placebo) After 3 Months of Treatment [ Time Frame: baseline to 12 weeks ]The Montgomery-Asberg Depression Rating Scale will be used to measure depressive symptoms to determine the efficacy of the study drugs. It has 10 items (subscales) ranging from 0-6. Therefore the total score ranges from 0-60, with lower scores indicating better outcomes. The subscales were summed for a total score.
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): NCT01134731
|United States, Alabama|
|Birmingham, Alabama, United States, 35294|
|Principal Investigator:||Richard C Shelton, M.D.||University of Alabama at Birmingham|