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| ID | Type | Description | Link |
|---|---|---|---|
| 1R01MH095776 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Mental Health (NIMH) | NIH |
| Wake Forest University Health Sciences | OTHER |
| University of Wisconsin, Madison | OTHER |
| Duke University |
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Epidemiologic reports have linked insomnia to suicidal ideation and suicide death. However, no studies have determined whether treating insomnia decreases the risk of suicidality. We have new data indicating that (1) the link between insomnia and suicidal ideation holds true in clinical trials of depressed insomniacs, (2) dysfunctional cognitions about sleep are related to suicidal ideas, and (3) treatment of insomnia with hypnotics leads to a reduction of suicidal ideation. We now propose to test whether cautious use of hypnotics in suicidal, depressed insomniacs may reduce suicide risk in a multi-site clinical trial.
Primary Aim: We will assess the effect of treating insomnia with hypnotic medication on the intensity of suicidal ideation in depressed outpatients with insomnia and suicidal ideation.
-Hypothesis 1. Treatment of depressed, insomniac and suicidal outpatients with open-label fluoxetine (FLX) and blinded zolpidem controlled release (ZOL) will reduce suicidal ideation more than treatment with FLX and blinded placebo.
Secondary Aim: We will examine whether reduced suicidal ideation in depressed insomniacs is mediated through reduced dysfunctional beliefs about sleep, reduced hopelessness, or fewer nightmares.
Tertiary Aim: We will confirm findings from our prior pilot studies that treatment of insomnia in depressed insomniacs leads to improvements in health-related quality of life, especially in women.
Exploratory Aim: We will archive actigraphy data to permit future examination to confirm our preliminary data that actigraphic activity decreases as suicidal ideation resolves.
Overview of the Need for and Management of a Collaborative Application: The sample sizes required to satisfy the Aims are relatively large, necessitating the pooled recruiting resources of 3 sites. Georgia Regents University (GRU) will serve both as the coordinating/data management site, as well as a recruiting site, with Duke and Wisconsin as recruiting sites. Project management will be coordinated through an Executive Committee of site principal investigators, under the supervision of a Data and Safety Monitoring Board.
Impact on the Field: This application has the potential to change providers' practice in the approach to treating insomnia in depressed patients with mild-moderate suicidal ideation. It may also reveal the mechanisms whereby insomnia increases the risk for suicidal ideation and behavior, and begin to examine whether there is an actigraphic "signature" for reductions in suicidal ideation. When these lessons are applied to the clinical world, they can be applied with low cost.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Zolpidem-CR | Active Comparator | Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks |
|
| Placebo | Placebo Comparator | Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Zolpidem-CR | Drug | Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Scale for Suicide Ideation Index (SSI) | This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation | Over 8 weeks of treatment |
| Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale | The suicide ideation scale of the C-SSRS is rated 0-5, with "0" meaning no suicidal ideation, "1" meaning a wish t be dead, "2" meaning non-specific active suicidal thoughts, "3" meaning active suicidal ideation with any methods but no plan or intent, "4" meaning active suicidal ideation with some intent but no specific plan, and "5" meaning active suicidal ideation with intent and a specific plan | 8 weeks of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Dysfunctional Beliefs and Attitudes About Sleep | The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep | 8 weeks of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale | This is one of the subscales of the Basis 32. It is self-administered. This subscale has 7 items, each scored 0-4. The totals score is an average of the scores of these 7 items. Higher scores indicate more difficulty with daily living and role functioning. | 8 weeks of treatment |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| William V McCall, MD, MS | Augusta University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Georgia Regents University | Augusta | Georgia | 30912 | United States | ||
| Duke University School of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39119911 | Derived | McCall WV, Mercado K, Dzurny TN, McCloud LL, Krystal AD, Benca RM, Rosenquist PB, Looney SW. Insomnia and the effect of zolpidem-extended-release on the sleep items of the Hamilton Rating Scale for Depression in outpatients with depression, insomnia, and suicidal ideation: Relationship to patient age. J Psychopharmacol. 2024 Sep;38(9):827-831. doi: 10.1177/02698811241268900. Epub 2024 Aug 9. | |
| 33884617 | Derived | Witt KG, Hetrick SE, Rajaram G, Hazell P, Taylor Salisbury TL, Townsend E, Hawton K. Psychosocial interventions for self-harm in adults. Cochrane Database Syst Rev. 2021 Apr 22;4(4):CD013668. doi: 10.1002/14651858.CD013668.pub2. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Zolpidem-CR | Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks |
| FG001 | Placebo | Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Zolpidem-CR | Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Scale for Suicide Ideation Index (SSI) | This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation | Posted | Least Squares Mean | Standard Error | units on a scale | Over 8 weeks of treatment |
|
8 weeks randomized care and 2 weeks of follow up after the end of randomized care
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Zolpidem-CR | Zolpidem 6.25 or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks Zolpidem-CR: Zolpidem 6.25 mg or 12.5 mg in tablet form at nighttime 15 minutes before bed for 8 weeks |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| pregnancy then miscarriage | Pregnancy, puerperium and perinatal conditions | Non-systematic Assessment | Despite being cautioned about the need for birth-control, a female participant nevertheless became pregnant (by her report), and shortly thereafter miscarried (by her report). She had a history of multiple prior miscarriages. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| cold symptoms and flu | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| William Vaughn McCall | Medical College of Georgia; Augusta University | 706-721-6719 | WMCCALL@augusta.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 8, 2014 | Mar 23, 2018 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D007319 | Sleep Initiation and Maintenance Disorders |
| D003863 | Depression |
| D059020 | Suicidal Ideation |
| ID | Term |
|---|---|
| D020919 | Sleep Disorders, Intrinsic |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D000077334 | Zolpidem |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| OTHER |
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| Placebo | Drug | Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks |
|
| Disturbing Dreams and Nightmares Severity Index (DDNSI) | This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares | 8 weeks of treatment |
| Beck Hopelessness Scale (BHS) | The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness | 8 weeks of treatment |
| Hamilton Rating Scale for Depression (HAM-D) | This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression | 8 weeks of treatment |
| Insomnia Severity Index (ISI) | The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia | 8 weeks of treatment |
| Actigraphy |
This device measures arm motion over time, reported as "average actigraphic activity Level". The scale is reported as a continuous measure ranging from 0-200, and reported as the average score for each hour for all 24-hours of the day. Higher score represent greater c=activity at that point in time |
| 8 weeks of treatment |
| Durham |
| North Carolina |
| 27710 |
| United States |
| Wake Forest University School of Medicine | Wake Forest | North Carolina | 27157 | United States |
| University of Wisconsin- Madison | Madison | Wisconsin | 53719 | United States |
| 32918323 | Derived | McCall WV, Benca RM, Rumble ME, Krystal AD. Blinding and bias in a hypnotic clinical trial. Hum Psychopharmacol. 2021 Jan;36(1):1-5. doi: 10.1002/hup.2757. Epub 2020 Sep 11. |
| 32329435 | Derived | Rumble ME, McCall WV, Dickson DA, Krystal AD, Rosenquist PB, Benca RM. An exploratory analysis of the association of circadian rhythm dysregulation and insomnia with suicidal ideation over the course of treatment in individuals with depression, insomnia, and suicidal ideation. J Clin Sleep Med. 2020 Aug 15;16(8):1311-1319. doi: 10.5664/jcsm.8508. |
| 31537089 | Derived | McCall WV, Benca RM, Rosenquist PB, Youssef NA, McCloud L, Newman JC, Case D, Rumble ME, Szabo ST, Phillips M, Krystal AD. Reducing Suicidal Ideation Through Insomnia Treatment (REST-IT): A Randomized Clinical Trial. Am J Psychiatry. 2019 Nov 1;176(11):957-965. doi: 10.1176/appi.ajp.2019.19030267. Epub 2019 Sep 20. |
| 31238203 | Derived | McCall WV, Benca RM, Rumble ME, Case D, Rosenquist PB, Krystal AD. Prevalence of obstructive sleep apnea in suicidal patients with major depressive disorder. J Psychiatr Res. 2019 Sep;116:147-150. doi: 10.1016/j.jpsychires.2019.06.015. Epub 2019 Jun 19. |
Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Scale for Suicide Ideation | This is the total score for the Scale for Suicide Ideation. It has 19 items, each scored 0-2, for a maximum of 38 points. Higher scores indicate worse suicidal ideation | Mean | Standard Deviation | units on a scale |
|
| Columbia Suicide Severity Rating Scale (C-SSRS) - suicide ideation scale | The suicide ideation scale of the C-SSRS is rated 0-5, with "0" meaning no suicidal ideation, "1" meaning a wish to be dead, "2" meaning non-specific active suicidal thoughts, "3" meaning active suicidal ideation with any methods but no plan or intent, "4" meaning active suicidal ideation with some intent but no specific plan, and "5" meaning active suicidal ideation with intent and a specific plan. | Mean | Standard Deviation | units on a scale |
|
| Hamilton Rating Scale for Depression -24 | This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression | Mean | Standard Deviation | units on a scale |
|
| Disturbing Dreams Nightmare Severity Index | This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares | Mean | Standard Deviation | units on a scale |
|
| Insomnia Severity Index | The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia | Mean | Standard Deviation | units on a scale |
|
|
|
| Primary | Columbia Suicide Severity Rating Scale (C-SSRS): the Suicidal Ideation Scale | The suicide ideation scale of the C-SSRS is rated 0-5, with "0" meaning no suicidal ideation, "1" meaning a wish t be dead, "2" meaning non-specific active suicidal thoughts, "3" meaning active suicidal ideation with any methods but no plan or intent, "4" meaning active suicidal ideation with some intent but no specific plan, and "5" meaning active suicidal ideation with intent and a specific plan | all evaluable randomized participants | Posted | Least Squares Mean | Standard Error | units on a scale | 8 weeks of treatment |
|
|
|
| Secondary | Dysfunctional Beliefs and Attitudes About Sleep | The Dysfunctional Beliefs and Attitudes About Sleep scale has 16 items and is self administered. Each item is scored 0-10. The total score is an average of the scores of the 16 items. Hence the range of the total score is also 0-10, with higher scores indicating greater dysfunctional beliefs about sleep | Posted | Least Squares Mean | Standard Error | units on a scale | 8 weeks of treatment |
|
|
|
| Secondary | Disturbing Dreams and Nightmares Severity Index (DDNSI) | This self-rated scale has 5 items, with asymmetric weighting of each item. The range of the total score is 0-37, with higher scores indicating worse nightmares | Posted | Least Squares Mean | Standard Error | units on a scale | 8 weeks of treatment |
|
|
|
| Secondary | Beck Hopelessness Scale (BHS) | The Beck Hopelessness Scale is self administered and has 20 'true/false' choices. Some items are reversed scored. The range of scores for the total is 0-20, with higher scores indicating greater hopelessness | Posted | Least Squares Mean | Standard Error | units on a scale | 8 weeks of treatment |
|
|
|
| Secondary | Hamilton Rating Scale for Depression (HAM-D) | This version of the Hamilton Rating Scale for Depression uses 24 items, with a possible total score ranging from 0-74, with higher scores indicating worse depression | Posted | Least Squares Mean | Standard Error | units on a scale | 8 weeks of treatment |
|
|
|
| Secondary | Insomnia Severity Index (ISI) | The Insomnia Severity Index is self rated. It has 7 items, each scored 0-4. Therefore the range of scores is 0-28, with higher scores indicating worse insomnia | Posted | Least Squares Mean | Standard Error | units on a scale | 8 weeks of treatment |
|
|
|
| Other Pre-specified | Basis-32 - the Daily Living and Role Functioning (DLRF) Subscale | This is one of the subscales of the Basis 32. It is self-administered. This subscale has 7 items, each scored 0-4. The totals score is an average of the scores of these 7 items. Higher scores indicate more difficulty with daily living and role functioning. | Posted | Least Squares Mean | Standard Error | units on a scale | 8 weeks of treatment |
|
|
|
| Other Pre-specified | Actigraphy | This device measures arm motion over time, reported as "average actigraphic activity Level". The scale is reported as a continuous measure ranging from 0-200, and reported as the average score for each hour for all 24-hours of the day. Higher score represent greater c=activity at that point in time | participants with depression, insomnia, and suicidality | Posted | Mean | Standard Error | units on a scale | 8 weeks of treatment |
|
|
|
| 0 |
| 51 |
| 1 |
| 51 |
| 31 |
| 51 |
| EG001 | Placebo | Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks Placebo: Placebo in tablet form at nighttime 15 minutes before bed for 8 weeks | 0 | 52 | 0 | 52 | 37 | 52 |
|
| nausea and diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| headache | Nervous system disorders | Non-systematic Assessment |
|
| Other | General disorders | Non-systematic Assessment |
|
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| D001523 |
| Mental Disorders |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D013405 | Suicide |
| D016728 | Self-Injurious Behavior |