A Phase 4 interventional study of paliperidone and lithium in Major Depressive Disorder and Suicidal Ideation, sponsored by University of Alabama at Birmingham. Completed at 1 site in United States. Open to participants aged 19 Years to 65 Years. Per ClinicalTrials.gov, last updated 2016-03-03.
Sponsored by University of Alabama at Birmingham · Phase 4, Interventional, and Treatment
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.
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.
4,845 studies on the registry are indexed under Depressive Disorder; 514 are open to participants now.
This study's enrollment of 54 is below the median of 80 across 3,999 interventional studies indexed under Depressive Disorder.
Browse Depressive Disorder studies →University of Alabama at Birmingham is the lead sponsor of 1,397 studies on the registry; 285 are open to participants now.
Of its 156 completed or terminated interventional studies of FDA-regulated products, 124 (79%) have results posted.
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Exclusion Criteria:
dose escalation , levels 1-5 daily dosing ranged from 1-5mg
Drug: paliperidone
dose escalation, level 1-5 daily dosing 300-1500mg
Drug: lithium
1-5 placebo capsules
Drug: Placebo
1-5 mg daily (QD)
300-1500mg QD
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
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.
Time frame: baseline to 12 weeks
Mean Score of Montgomery-Asberg Depression Scale of Three Treatment Groups (Paliperidone, Lithium and Placebo) After 3 Months of Treatment
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.
Time frame: baseline to 12 weeks
Participants were male and female, aged 19- 65 years old, recruited as outpatients from the general public.
| Milestone | Paliperidone | Lithium | Placebo |
|---|---|---|---|
| Started | 23 | 21 | 10 |
| Completed | 10 | 10 | 2 |
| Not completed | 13 | 11 | 8 |
| Withdrew: Adverse event | 3 | 2 | 1 |
| Withdrew: Physician decision | 2 | 2 | 2 |
| Withdrew: Lack of efficacy | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 3 | 3 | 1 |
| Withdrew: Lost to follow-up | 5 | 4 | 3 |
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.
| units on a scale | Paliperidone | Lithium | Placebo |
|---|---|---|---|
| Mean Score of Beck Scale for Suicidal Ideation of Three Treatment Groups (Paliperidone, Lithium and Placebo) After 3 Months of Treatment | 22.1 ± 8.6 | 22.1 ± 8.6 | 21.3 ± 9.6 |
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.
| units on a scale | Paliperidone | Lithium | Placebo |
|---|---|---|---|
| Mean Score of Montgomery-Asberg Depression Scale of Three Treatment Groups (Paliperidone, Lithium and Placebo) After 3 Months of Treatment | 37.5 ± 5.6 | 39.6 ± 4.1 | 39.2 ± 8.1 |
Collected over Adverse event reporting started 3/1/2011 and stopped 10/15/2014. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Paliperidone | — | 0/23 (0%) | 0/23 (0%) |
| Lithium | — | 0/21 (0%) | 0/21 (0%) |
| Placebo | — | 0/10 (0%) | 0/10 (0%) |
| Age, Categorical(Participants) | Paliperidone 1-5mg | Lithium 600-1500mg | Placebo 1-5 Capsules | Total |
|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 23 | 21 | 10 | 54 |
| >=65 years | 0 | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Paliperidone 1-5mg | Lithium 600-1500mg | Placebo 1-5 Capsules | Total |
|---|---|---|---|---|
| Female | 23 | 21 | 10 | 54 |
| Male | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Paliperidone 1-5mg | Lithium 600-1500mg | Placebo 1-5 Capsules | Total |
|---|---|---|---|---|
| United States | 23 | 21 | 10 | 54 |
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University of Alabama at Birmingham