Cognitive Behavioral Therapy and Trazodone Effects on Sleep and Blood Pressure in Insomnia

Cognitive Behavioral Therapy and Trazodone Effects on Sleep and Blood Pressure in Insomnia Phenotypes Based on Objective Sleep Duration: A Sequential Cohort/Randomized Controlled Trial

Individuals who have insomnia with short sleep duration (ISS) differ from individuals who have insomnia with normal sleep duration (INS) in terms of health risks (i.e., hypertension) and treatment response. This study will examine whether patients with ISS and INS demonstrate a differential response to two common insomnia treatments. One is behavioral, Cognitive Behavioral Therapy for Insomnia (CBT-I). The other is a widely prescribed, non-habit-forming medication, trazodone used at a low dose. The investigators' findings could lead to evidence-based treatment guidelines that help clinicians more effectively match treatments to insomnia patients and reduce associated health problems.

Study Overview

• Status: Recruiting
• Conditions: Insomnia; Blood Pressure; Insomnia Chronic; Insomnia, Primary; Blood Pressure, High
• Intervention / Treatment: Behavioral: Cognitive Behavioral Treatment for Insomnia (CBT-I); Other: Placebo; Drug: Trazodone

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Carrie Criley; Phone Number: 717-531-4123; Email: ccriley@pennstatehealth.psu.edu

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1V 0A6
      • Recruiting
      • Université Laval
      • Contact: Manon Lamy; Phone Number: 412467 418 656-2131; Email: manon.lamy@psy.ulaval.ca
• United States
  • Colorado
    • Denver, Colorado, United States, 80206-2761
      • Recruiting
      • National Jewish Health
      • Contact: Roxane Horberg; Phone Number: 303-270-2850; Email: horbergr@njhealth.org
      • Contact: Rachel Johnson; Phone Number: 303 398-1058; Email: johnsonr@njhealth.org
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Recruiting
      • Penn State University
      • Contact: Carrie Criley; Phone Number: 717-531-4123; Email: ccriley@pennstatehealth.psu.edu
    • Pittsburgh, Pennsylvania, United States, 15213-3203
      • Recruiting
      • University of Pittsburgh
      • Contact: Laurie Brar; Phone Number: 412-723-7998; Email: brarlk@upmc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 or older
• Able to read and effectively communicate in English at the United States sites or able to read and effectively communicate in English or French at the Canadian site.
• Meets criteria for chronic insomnia
• Body Mass Index (BMI) 18.5 kg/m2 and higher

Exclusion Criteria:

• Age < 18
• Unable to read and effectively communicate in English at the United States sites or able to read and effectively communicate in English or French at the Canadian site.
• Unwilling to share email address/cell phone number to accept survey links.
• Life time diagnosis of psychotic or bipolar disorder
• History of severe apnea or an Apnea Hypopnea Index (AHI) ≥15 that is not currently treated with Positive Airway Pressure (PAP) therapy, an oral device or an implanted device, or was not treated with surgery or weight loss.
• Started new or changed treatment for sleep apnea in the past three months
• Does not meet criteria for chronic insomnia
• Meets criteria for narcolepsy or hypersomnia disorder
• Meets criteria for circadian rhythm disorder (including night shift work)
• Unstable medical conditions that would make participation unsafe or unfeasible
• Falls resulting in hospitalization, significant injury or fracture within past 12 months
• 2 hospitalizations or emergency room visits within past 12 months for chronic conditions
• Active chemotherapy or radiation therapy for cancer
• Lifetime diagnoses/treatment of chronic renal failure, hepatic insufficiency, chronic heart failure
• Does not agree to refrain from other treatments for insomnia beyond what is offered in this study
• BMI less than 18.5
• Substance abuse or dependence in the past 12 months
• Current use of prescription or over the counter medications taken for sleep greater than 2 times per week
• Current use of systemic corticosteroids or opiate medications
• Current pregnancy or breastfeeding; plans to get pregnant or unwillingness to use birth control for the length of the study
• Current use of medications contraindicated with trazodone
• Sleep apnea or periodic leg movement disorder as determined by sleep study
• Blood Pressure levels defined as seated SBP greater than 180 or DBP greater than 110 mmHg
• EKG corrected QT interval greater than or equal to 500 ms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Subjects treated with Cognitive Behavior Treatment for Insomnia (CBT-I) with placebo; Subjects with insomnia treated with Cognitive Behavior Treatment for Insomnia (CBT-I) for 8 weeks, then non-remitting subjects received placebo for 8 weeks.	Behavioral: Cognitive Behavioral Treatment for Insomnia (CBT-I); Subjects will receive therapy for 8 weeks; Other: Placebo; Non-remitting subjects will receive placebo for 8 weeks
Active Comparator: Subjects treated with Cognitive Behavior Treatment for Insomnia (CBT-I) with Trazodone; Subjects with insomnia treated with Cognitive Behavior Treatment for Insomnia (CBT-I) for 8 weeks, then non-remitting subjects received trazodone for 8 weeks.	Behavioral: Cognitive Behavioral Treatment for Insomnia (CBT-I); Subjects will receive therapy for 8 weeks; Drug: Trazodone; Non-remitting subjects will receive Trazodone (dosage) for 8 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission of insomnia symptoms following Cognitive Behavioral Therapy for Insomnia (CBT-I)	Based on Insomnia Severity Index (ISI) published criteria; 0-28, with 0 being mild and 28 being severe	9 weeks
Remission of insomnia symptoms following trazodone/placebo Randomized Controlled Trial (RCT)	Based on Insomnia Severity Index (ISI) published criteria; 0-28, with 0 being mild and 28 being severe	9 weeks
Remission of insomnia symptoms 6 months following completion of CBT-I Or RCT Treatment	Based on Insomnia Severity Index (ISI) published criteria; 0-28, with 0 being mild and 28 being severe	35 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insomnia Severity Index (ISI) Score following CBT-I	0-28, with 0 being mild and 28 being severe	9 weeks
Polysomnography (PSG) Sleep efficiency following Cognitive Behavioral Therapy for Insomnia (CBT-I)	Polysomnography (PSG) Sleep efficiency measured as a percentage of time asleep during sleep study	9 weeks
Actigraphy Sleep efficiency following Cognitive Behavioral Therapy for Insomnia (CBT-I)	Actigraphy Sleep efficiency measured as estimated sleep time at home (2 week period)	9 weeks
Evening Cortisol levels following CBT-I	Cortisol levels measured in saliva collected following CBT-I	9 weeks
Insomnia Severity Index (ISI) Score following RCT	0-28, with 0 being mild and 28 being severe	9 weeks
PSG Total Sleep Time (TST) following RCT	PSG Total Sleep Time measured in minutes asleep during sleep study following RCT	9 weeks
Actigraphy Total Sleep Time (TST) following RCT	Actigraphy Total Sleep Time measured in minutes asleep during home study following RCT	9 weeks
Home Blood Pressure (HBP) Morning Systolic Blood Pressure (SBP)	Morning SBP Blood Pressure Readings measured at home (7 day period)	9 weeks
Home Blood Pressure (HBP) Morning Diastolic Blood Pressure (DBP)	Morning DBP Blood Pressure Readings measured at home (7 day period)	9 weeks
Evening Cortisol levels following RCT	Cortisol levels measured in saliva collected following RCT	9 weeks
Evening Cortisol levels 6 months following completion of CBT-I or RCT Treatment	Cortisol levels measured in saliva 6 months following CBT-I Or RCT Treatment	35 weeks

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Alexandros Vgontzas, MD, Professor, Psychiatry

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2024
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): May 31, 2028

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: February 26, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 6, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: sleep; insomnia; sleep disorder
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypertension; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Pyridones; Trazodone
• Other Study ID Numbers: STUDY00022285; 1UG3HL161342-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The investigators have extensive experience preparing data and documentation to be available for public. They agree to abide by the principles for sharing research resources described by the National Heart, Lung, Blood Institute (NHLBI). A copy of the data will be uploaded to the NHLBI Biologic Specimen and Data Repositories Information Coordinating Center (BioLINCC) repository. The datasets will not include any personal identifiers related to participants or clinical sites. Dates will be de-identified through a date-shifting algorithm to mask actual dates while maintaining a relation to the epoch in which events occurred. Data tables will be exported in comma-separated format, readable by statistical software. Variable dictionaries and code books, detailing variable description, format, value domain and labels, will be produced. Raw data files for polysomnogram/actigraphy/cortisol will also be made available, ensuring that data are linkable to study data and data are de-identified.
• IPD Sharing Time Frame: Data collected for aim 1 (an observational study) and aim 2 (a randomized clinical trial) will be made available no more than 3 years after the completion of the last follow-up assessment. Data will be submitted to the Program Officer and uploaded to the NHLBI BioLINCC repository no later than 3 years after the end of clinical activity or 2 years after the main outcomes paper is published, whichever comes first.
• IPD Sharing Access Criteria: NHLBI BioLINCC repository
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No