Optimizing Long-Term Outcomes for Winter Depression With CBT-SAD and Light Therapy

• ClinicalTrials.gov Identifier: NCT03691792
• Recruitment Status: Recruiting
• First Posted: October 2, 2018
• Last Update Posted: October 5, 2021
• Sponsor: University of Vermont
• Collaborators: University of Pittsburgh; University of Maryland, College Park
• Information provided by (Responsible Party): Kelly Rohan, University of Vermont

Study Description

Brief Summary:

Major depression is a highly prevalent, chronic, and debilitating mental health problem with significant social cost that poses a tremendous economic burden. Winter seasonal affective disorder (SAD) is a subtype of recurrent major depression that affects 5% of the population (14.5 million Americans), involving substantial depressive symptoms for about 5 months of each year during most years, beginning in young adulthood.

Condition or disease	Intervention/treatment	Phase
Seasonal Affective Disorder	Behavioral: Cognitive-Behavioral Therapy (CBT-SAD); Other: Light Therapy	Phase 2; Phase 3

Detailed Description:

Winter seasonal affective disorder (SAD) is a subtype of recurrent depression involving major depressive episodes during the fall and/or winter months that remit each spring. The central public health challenge in the management of SAD is prevention of winter depression recurrences. This application focuses on two SAD treatments that each work for some patients: light therapy (LT) and a SAD-tailored group cognitive-behavioral therapy (CBT-SAD). LT is the acute SAD treatment with the most substantial evidence to support its efficacy. Correction of circadian phase is LT's established target and mechanism. In our recently completed R01-level efficacy trial, post-treatment outcomes for CBT-SAD and LT were very similar, but CBT-SAD was associated with fewer depression recurrences over 2-year followup than LT (27.3% in CBT-SAD vs. 45.6% in LT). CBT-SAD engaged and altered a specific mechanism of action, seasonal beliefs, which improved at twice the rate during CBT-SAD compared to LT, and this improvement was associated with lower risk for recurrence following CBT-SAD. This confirmatory efficacy R01 will apply the experimental therapeutics approach to determine how each treatment works when it is effective and to identify the best candidates for each. We will ascertain whether theoretically-derived candidate biomarkers of each treatment's target and effect are prescriptive of better outcomes in that treatment vs. the other. Biomarkers of LT's target and effect include circadian phase angle difference (PAD) and the post-illumination pupil response (PIPR). Biomarkers of CBT-SAD's target and effect include pupil dilation and sustained gamma band EEG responses to seasonal words, which are hypothesized to reflect less engagement with seasonal stimuli following CBT-SAD and corroborate with the established target of seasonal beliefs. In addition to determining change mechanisms, we will test the efficacy of a "switch" decision rule upon recurrence to inform clinical decision-making in practice. We will randomize 160 adults with SAD to 6-weeks of CBT-SAD or LT in Winter 1; follow subjects in Winter 2; and, if a depression recurrence occurs, cross them over into the alternate treatment (i.e., switch from LT to CBT-SAD or CBT-SAD to LT). All subjects will be followed in Winter 3. Biomarker assessments will occur at pre-, mid-, and post-treatment in Winter 1, at Winter 2 followup (and again at mid-/post-treatment for those crossed-over), and at Winter 3 followup. Consistent with NIMH's priorities for demonstrating target engagement at the level of RDoC-relevant biomarkers, this work aims to confirm the targets and mechanisms of LT and CBT-SAD to maximize the impact of future dissemination efforts.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: head-to-head RCT
• Masking: Single (Outcomes Assessor)
• Masking Description: Outcomes are rated on a semi-structured interview by raters blind to treatment assignment.
• Primary Purpose: Treatment
• Official Title: Optimizing Long-Term Outcomes for Winter Depression With CBT-SAD and Light Therapy: Confirming the Targets, Mechanisms, and Treatment Sequence
• Actual Study Start Date: September 1, 2018
• Estimated Primary Completion Date: February 28, 2023
• Estimated Study Completion Date: February 28, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cognitive-Behavioral Therapy (CBT-SAD); 12 1.5-hour group sessions at a rate of 2 sessions per week over 8 weeks.	Behavioral: Cognitive-Behavioral Therapy (CBT-SAD); 12 group sessions over 6 weeks; Other Name: CBT-SAD
Active Comparator: Light Therapy; 6 weeks of daily light therapy at home, using a 10,000-lux light box beginning at 30 minutes upon waking, with dose subsequently adjusted per treatment algorithm.	Other: Light Therapy; 10,000-lux initiated at 30 min upon waking and adjusted per treatment algorithm, continuing for 6 weeks

Outcome Measures

Primary Outcome Measures :

1. Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder Version (SIGH-SAD) [ Time Frame: past 1 week ]
   Semi-structured interview of depressive symptoms
2. Beck Depression Inventory-Second Edition (BDI-II) [ Time Frame: past 2 weeks ]
   self-report measure of depressive symptoms

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Principle DSM-5 diagnosis of Major Depression, Recurrent, with Seasonal Pattern. -Meet Structured Interview Guide for the Hamilton Rating Scale for Depression-Seasonal Affective Disorder Version (SIGH-SAD) criteria for a current SAD episode (see below).
• No use or stable use of antidepressants (i.e., a consistent dose of the same medication maintained for > 4 weeks with no plans to change).

Exclusion Criteria:

• Current or past light therapy or CBT for SAD.
• Presence of a comorbid Axis I disorder that requires immediate treatment (i.e., bipolar disorder, psychotic disorders, substance use disorder).
• Acute and serious suicidal intent.
• Planned absences of >1 week from the area through March.
• History of conditions that are known contra-indications to LT, including conditions associated with toxicity of bright light to the retina (i.e., macular degeneration or any retinopathy).

Contacts and Locations

Contacts

Contact: Kelly J Rohan, Ph.D.; (802) 656-0798; kelly.rohan@uvm.edu

Locations

United States, Vermont

University of Vermont, Psychology Department; Recruiting

Burlington, Vermont, United States, 05405-0134

Contact: Kelly J Rohan, Ph.D. 802-656-0798 kelly.rohan@uvm.edu

Principal Investigator: Kelly J Rohan, Ph.D.

Sponsors and Collaborators

University of Vermont

University of Pittsburgh

University of Maryland, College Park

Investigators

• Principal Investigator: Kelly J Rohan, Ph.D.; University of Vermont

More Information

• Responsible Party: Kelly Rohan, Professor, University of Vermont
• ClinicalTrials.gov Identifier: NCT03691792
• Other Study ID Numbers: R01MH112819 ( U.S. NIH Grant/Contract )
• First Posted: October 2, 2018
• Last Update Posted: October 5, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Study data will be provided to the NIMH Data Archive
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: After publication of the study results.
• URL: https://data-archive.nimh.nih.gov/

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kelly Rohan, University of Vermont:

cognitive-behavioral therapy; light therapy; biomarkers; treatment mechanisms

Additional relevant MeSH terms:

Mood Disorders; Seasonal Affective Disorder; Mental Disorders; Depressive Disorder