Clinical trial NCT03764683: Suvorexant (Belsomra) for the Treatment of Bipolar Depression With Insomnia
Official title: A Double-Blind Sequential Parallel Study of Suvorexant (Belsomra) for the Treatment of Bipolar Depression With Insomnia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Bipolar Disorder
Insomnia
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2018-12-05
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The investigators are proposing the use of SPCD for this study. The Sequential Parallel Comparison Design aims to reduce the impact of high placebo response and decrease sample size. The design has been accepted by and published on by FDA. The SPCD model has two relatively short phases of treatment of equal duration. Only non-responders to placebo (P) during the first phase are included in the analyses of the second phase. Randomization is unbalanced (for example, a 2:3:3 assignment of DD, PP, and PD).
Primary purpose: TREATMENT

Brief summary: The investigators are doing this research study to find out if suvorexant (Belsomra) can help people with bipolar depression when added to their usual treatment. The investigators also want to find out if suvorexant (Belsomra) is safe to take without causing too many side effects in people with bipolar disorder.

Suvorexant (Belsomra) is approved by the U.S. Food and Drug Administration (FDA) to treat insomnia. It has not yet been studied in people with bipolar disorder who have problems sleeping.

This research study will compare suvorexant (Belsomra) to placebo. The placebo looks exactly like suvorexant (Belsomra), but contains no suvorexant (Belsomra). During this study participants may get a placebo instead of suvorexant (Belsomra). Placebos are used in research studies to see if the results are due to the study drug or due to other reasons.

This study has two parts, each lasting 6 weeks. During each part, participants may receive either Belsomra or placebo. Some participants will receive suvorexant for both parts, some will receive placebo for both parts, and others will receive suvorexant during one part and placebo during the other part. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons.

This study is open to people with bipolar disorder who have trouble sleeping. Bipolar disorder is a brain disorder associated with episodes of mood swings ranging from depressive lows to manic highs.

About 80 subjects will take part in this research study. All subjects will be enrolled at Massachusetts General Hospital (MGH).


Eligibility criteria: Inclusion Criteria:

1. Men or women between the ages of 18 and 75.
2. DSM V diagnosis of Bipolar Disorder Type I and II.
3. Ability to sign the Informed Consent Form.
4. Not taking an antidepressant medication within the past 14 days.
5. Meets criteria for a current major depressive episode as defined and operationalized by the MINI.
6. Patients must have a 10-item MADRS Rating Scale for Depression score ≥ 16 and item 4 (Reduced sleep) score ≥ 4 during the screening phase and at baseline to qualify for inclusion.
7. Scores \>15 on the QIDS-SR.
8. Does not meet criteria for current hypomanic or manic episode as defined and operationalized by the MINI 7.0.2.
9. Patients must be stable on their bipolar medications for at least 1 month (4 weeks) prior to screening.

Exclusion Criteria:

1. Unable to sign the Informed Consent Form.
2. Declines to participate.
3. DSM-V diagnosis of Psychosis, Schizophrenia, Schizoaffective Bipolar type.
4. Meets criteria for current hypomanic or manic episode as defined and operationalized by the MINI.
5. Pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (e.g. oral contraceptives, intrauterine device, barrier methods, or total abstinence from intercourse; Depo Provera is acceptable if it is started 3 months prior to enrollment).
6. Patients who are a serious suicide or homicide risk, suicidal exclusion criteria as follows:

   1. Suicidal ideation associated with actual intent and a method or plan in the past year: "Yes" answers on items 4 or 5 of the C-SSRS
   2. Previous history of suicidal behaviors in the past one year: "Yes" answer (for events that occurred in the past year) to any of the suicidal behavior items of the C-SSRS. (Non-suicidal self-injurious behavior is not included unless in the investigator's judgment it is indicated).
   3. Any lifetime history of serious or recurrent suicidal behavior.
   4. In the investigator's judgment further risk assessment or exclusion due to suicidality is required.
7. Unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
8. The following DSM-V diagnoses: 1) organic mental disorders; 2) substance use disorders, including alcohol but excluding tobacco, active within the 3 months; 3) schizophrenia; 4) delusional disorder; 5) psychotic disorders not elsewhere classified; 6) schizoaffective disorder; 7) acute bereavement; 9) severe borderline or antisocial personality disorder.

   a. Subjects who have a positive urine drug screen which cannot be explained by prescribed medications, or for which patients do not have a valid prescription for a valid medical reason.
9. Patients meeting criteria for current bipolar mixed episode as defined and operationalized by the MINI.
10. Patients with mood congruent or mood incongruent psychotic features.
11. Clinical or laboratory evidence of hypothyroidism.
12. Patients previously treated with Suvorexant (Belsomra)
13. Patients who have taken an investigational psychotropic drug within the last 60 days.
14. Standard multivitamins with or without minerals will be allowed (with no more than 400 mcg folate) if initiated at least 12 weeks prior to Baseline. Dietary supplements with putative CNS activity will be excluded including SAMe, St. John's Wort, DHEA, Inositol, and Ginko biloba.
15. Previous treatment with the following procedures: ECT, vagus nerve stimulation, or deep brain stimulation.

Primary outcomes:
measure: Change in sleep quality via Pittsburgh Sleep Quality Index (PSQI)
timeFrame: The PSQI will assess change in perceived sleep quality from Week 1 to Week 8 to Week 10 to Week 12 to Week 14.
measure: Change in depressive symptoms via the Bipolar Inventory of Symptoms Scale (BISS)
timeFrame: The BISS will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.
measure: Change in manic symptoms via the Bipolar Inventory of Symptoms Scale (BISS)
timeFrame: The BISS will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.
measure: Change in psychosocial functioning via Quality of Life Satisfaction Questionnaire (Q-LES-Q)
timeFrame: The Q-LES-Q will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.
Secondary outcomes:
measure: Change in insomnia measured via Insomnia Severity Index (ISI)
timeFrame: This will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.
measure: Change in bipolar symptom severity via Clinical Global Impressions - Severity (CGI-S)
timeFrame: This will be administered at Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.
measure: Change in suicidal ideation score on The Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: This will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.
measure: Change in functioning via MGH Cognitive and Physical Functioning Questionnaire (MGH-CPFQ)
timeFrame: This will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.
measure: Change in depressive symptoms via Quick Inventory of Depression Symptomatology-Self Report (QIDS-SR)
timeFrame: This will be administered at Screen visit, Baseline visit (Week 0), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, and Week 14.
Other outcomes:
Locations:
Study officials:
affiliation: Massachusetts General Hospital
name: Gustavo Kinrys, MD
role: PRINCIPAL_INVESTIGATOR
References: