Stepped-Care Telehealth for Distress in Cancer Survivors

Study Overview
=================
Brief Summary
-----------------
Mental health issues in post-treatment adult cancer survivors are associated with multiple adverse outcomes and may represent a cancer health disparity for rural survivors. The purpose of this study is to test a stepped-care approach tailored to symptom severity based on recent American Society of Clinical Oncology guidelines for reducing emotional distress (anxiety and/or depressive symptoms) and improving secondary outcomes (sleep disturbance, fatigue, fear of recurrence, quality of life) in rural, post-treatment cancer survivors in community oncology settings and to examine intervention costs. The resultant intervention will have great potential for widespread dissemination since it will be manualized, delivered by telephone, and comprised of modules to allow customized treatments for individuals with different cancer types.

Detailed Description
-----------------
Noting the need for evidence-based cancer survivorship care, the American Society of Clinical Oncology (ASCO) published guidelines for screening, assessment, and care of psychosocial distress (anxiety, depression) in adults with cancer. These guidelines recommend screening all adults with cancer for distress and treating those with moderate or severe symptoms using a stepped-care approach tailored to distress severity. While these guidelines apply to survivors with all cancer types across the cancer treatment and survivorship continuum, we have chosen to focus on survivors with non-metastatic breast, colorectal, prostate, uterine, and cervical cancers , as well as those with any stage lymphoma (Hodgkin's or non-Hodgkin's). Further, we have focused on the post-treatment survivorship period 6 months-5 years post-treatment because distress may be more likely to be assessed and addressed after treatment completion. A significant minority of post-treatment survivors is at risk for anxiety and depression symptoms during the five years following the end of treatment and accessible interventions are needed to treat them. The purpose of this study is to test a method of implementing this stepped-care approach in community oncology practices caring for cancer survivors, using self-directed and stepped-care telehealth approaches based on cognitive-behavioral theory. Our approach is based on a previous trial of telephone-based cognitive behavioral therapy for rural older adults with Generalized Anxiety Disorder (NIMH 1R01MH083664: The Tranquil Moments Study; PI: Brenes), which has demonstrated high acceptability and efficacy for reducing anxiety, worry, and depressive symptoms in a rural geriatric population. This protocol adapts the methods of the previous trial to bring psychosocial care to underserved cancer survivors, many of whom have minimal or no access to mental health providers. Cancer survivors will be recruited through multiple NCI Community Oncology Research Program (NCORP) sites through the NCI-funded Wake Forest NCORP Research Base (WF NCORP RB). We will obtain data on feasibility, outcome variability, and efficacy for designing a subsequent fully powered randomized controlled trial (RCT) assessing the effects of the intervention on distress in cancer survivors. In the planned larger study, we anticipate that this intervention will: (a) reduce treatment barriers for post-treatment cancer survivors; (b) enhance availability of psychosocial treatment (through use of telephone sessions and a workbook); and (c) result in reductions in anxiety and depressive symptoms in cancer survivors.

Official Title
-----------------
Stepped-Care Telehealth for Distress in Cancer Survivors

Conditions
-----------------
Anxiety, Depressive Symptoms, Sleep Disturbance, Recurrent Disease, Fatigue, Quality of Life, Cancer

Intervention / Treatment
-----------------
* Other: Severe Anxiety/depression: High Intensity Stepped Care
* Other: Moderate Anxiety/depression: Low Intensity Stepped care
* Other: Enhanced Usual Care Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥18 years Score ≥10 on the GAD-7 and/or a score ≥8 on the PHQ-9, indicating clinically significant anxiety or depressive symptoms, respectively. Past history of treated Stage I, II, or III (newly diagnosed or recurrent) breast, colorectal, prostate, gynecologic (to include uterine and cervical) cancers and non-Hodgkin's lymphoma. 6-60 months post-treatment (surgery, chemotherapy, and/or radiation therapy) for cancer. Time frame applies to most recent completion of treatment if participant had a cancer recurrence. It is acceptable to be on maintenance or hormonal therapies. Participant resides in California, Georgia, Illinois, Kansas, Michigan, Minnesota, Missouri, New Mexico, North Carolina, North Dakota, South Carolina, Virginia, Tennessee, or Wisconsin Study-trained therapist in the state where the participant resides. Must be able to speak and understand English. Must have access to a telephone Exclusion Criteria: Current psychotherapy [regular appointment(s) with a psychologist, counselor, or therapist within the last 30 days prior to randomization]. Self-reported active alcohol or substance abuse within the last 30 days. Past history of prostate cancer or non-Hodgkin's lymphoma with only active surveillance (i.e., no surgery, chemotherapy, or radiation therapy). Diagnosis of a second malignancy (except for non-melanoma skin cancers) after a previous diagnosis of breast, colorectal, gynecologic cancers and non-Hodgkin's lymphoma Progressive cancer (must be considered no evidence of disease or stable) Self -reported history of a diagnosis of dementia from a healthcare provider. Self -reported psychotic symptoms in the last 30 days prior to randomization Active suicidal ideation (currently reported suicidal plan and intent). Any change in psychotropic medications within the last 30 days. Hearing loss that would preclude participating in telephone sessions (determined by brief hearing assessment administered by research staff) Failure/inability/unwillingness to provide names and contact information for two family members or friends to serve as emergency contacts during the course of the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be stratified by baseline score ≥15 on the GAD-7 and/or on the PHQ-9, indicating severe significant anxiety or depressive symptom. Participants with moderate symptoms only (10-14 on the PHQ-9 and/or 8-14 on the GAD-7) will be block randomized to either the low-intensity stepped care or to the enhanced usual care (EUC control). Participants with moderate to severe symptoms will be block randomized to either the high-intensity stepped care intervention or the EUC control. Block sizes will be chosen randomly to ensure that future assignments cannot be inferred from previous ones.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Moderate Anxiety/depression: Low Intensity Stepped care<br>participants with moderate symptoms (PHQ-9-14; GAD-7: 10-14) will be randomized to either low-intensity stepped care or enhanced usual care. Stepped care consist of a self-guided cognitive behavioral therapy (CBT) workbook to reduce anxiety and depressive symptoms and biweekly (every two weeks) check-in calls from research staff to assess changes in symptom severity/immediate need for psychiatric treatment and provide minimal support. | Other: Moderate Anxiety/depression: Low Intensity Stepped care<br>* The stepped care Telehealth low intensity intervention is tailored to participants with moderate anxiety and depression. Ppts randomized to this group will receive a self-guided CBT workbook and biweekly (every 2 weeks) check-in calls from a research staff person to assess changes in symptom severity and need for treatment/support.<br>|
| Experimental: Severe Anxiety/depression: High Intensity Stepped Care<br>Participants with severe symptoms (PHQ-9: 15-27; GAD-7: 15-21) will be randomized to high intensity stepped care (consist of a CBT workbook with accompanying psychotherapy by a Master's-level therapist delivered by telephone) or EUC. EUC consist of information about referrals/resources locally and nationally. | Other: Severe Anxiety/depression: High Intensity Stepped Care<br>* The stepped-care Telehealth high intensity intervention is tailored to participants with severe anxiety and depression. Ppts randomized to this group will have 12 weekly psychotherapy sessions delivered by phone with a licensed therapist. Participants will also receive a CBT (cognitive behavioral therapy) workbook including daily exercises to supplement understanding.<br>|
| Active Comparator: Enhanced Usual Care Control (EUC)<br>Participants randomized to EUC will receive information about local referrals/resources (support groups, mental health providers, etc.). They will also be provided Facing Forward: Life after Cancer Treatment, a book developed by the NCI to assist with transition from active treatment to survivorship. Participants will receive information on self-help workbooks for anxiety & depressive symptoms. EUC control will receive a copy of the CBT workbook on completion of the study. | Other: Enhanced Usual Care Control<br>* Participants with moderate to severe anxiety/depression that are randomized to Enhanced Usual Care Control (EUC) will receive information about referrals/resources in their local area (support groups, mental health providers), NCI materials (Facing Forward: Life after Cancer Treatment, self-help workbooks, copy of the CBT (cognitive behavioral therapy) workbook on completion of the study.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Study Intervention Measured by Retention | Study retention will be estimated by the number of participants who complete the Week 7 and 13 visits | Randomization through completion of study at week 13 | 
| Feasibility of Study Intervention Measured by Adherence to Intervention | Intervention adherence will be estimated as the mean proportion of therapy (high-intensity intervention) or check-in (low-intensity intervention) sessions each participant completes. | Randomization through completion of study at week 13 | 
| Feasibility of Study Intervention Measured by Recruitment Rate | Recruitment rate will be determined by the number of eligible participants who met all eligibility criteria and percent who agreed to participate. | Screening through end of study at week 13 | 
| Feasibility of Study Intervention Measured by Accrual Rate | The accrual rate is determined by dividing the overall number of participants recruited in each arm by the total span of 38 months between the start of the first screening for enrollment and the time the study closed to accrual. | Start of study screening time to end of study accrual | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal Changes in the Generalized Anxiety Disorder (GAD)-7 Score for Anxiety From Baseline to 13 Weeks | The Generalized Anxiety Disorder (GAD) -7 is a self-report measure of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) symptoms of Generalized Anxiety Disorder (GAD). Longitudinal changes in the GAD-7 will be measured in participants to evaluate the effectiveness of the intervention in reducing anxiety. Patients select 1 of 4 numbers with 0 indicating not all, to 3 indicating nearly everyday. The first 7 questions are summed to create a total score ranging from 0 to 21. Higher scores reflect greater anxiety severity. Scores above 10 are considered to be in the clinical range. GAD-7 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe anxiety, respectively. | Screening or baseline (if >30 days since screening), Week 13 | 
| Longitudinal Changes in the Patient Health Questionnaire (PHQ-9) Score for Depression From Baseline to 13 Weeks | The PHQ-9 is a self-report measure of DSM-IV symptoms of Major Depressive Disorder where participants rate how often they experienced 9 symptoms over past 2 weeks. Patients select 1 of 4 numbers with 0 indicating not all, to 3 indicating nearly everyday. Longitudinal changes in the PHQ-9 will be measured in participants to evaluate the effectiveness of the intervention in reducing depression. The possible range is 0-27. A larger score represents more severe depression level. | Screening or baseline (if >30 days since screening), Week 13 | 
| Number of Participants With Moderate of Severe Depression (PHQ-9) or Anxiety (GAD-7) at 13 Weeks | A combined variable will be created that indicates if a participant had moderate/severe depression or anxiety at mid- or post-intervention. This is defined as either PHQ-9 or GAD-7 greater than or equal to 15. | Week 13 | 
| Longitudinal Changes in the Insomnia Severity Index (ISI) From Baseline to 13 Weeks. | Measure Description: The Insomnia Severity Index (ISI) is 7-item self-report measure of type and severity of insomnia symptoms, including problems with sleep onset, sleep maintenance, or early morning awakening; satisfaction with current sleep pattern; interference with daily functioning; noticing impairment attributed to sleep problems; and level of concern or distress caused by the sleep problem. Each of the seven items is scored on a 5-point scale, ranging from 0 (lowest) to 4 (highest). The sum of the scores for all seven items yields a total score, which falls within a range of 0 to 28. A higher score indicates a greater level of sleep impairment. | Baseline (Week 0), Week 13 | 
| Longitudinal Changes in the PROMIS Fatigue Scale From Baseline to 13 Weeks | The Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 8a is a measure of the experience of fatigue and the impact of fatigue on activities across multiple domains. There are eight items rated on a scale of 1(never) to 5 (always) based on how often fatigue was experienced over the last 7 days. The sum of these eight items ranges from a minimum of 8 to a maximum of 40, with higher scores representing more fatigue. This total score is then converted into a t-score based on the PROMIS 8a adult conversion table. The smallest t score is 33.1 and the largest t score is 77.8. A higher t score indicates greater fatigue. | Baseline (Week 0), Week 13 | 
| Longitudinal Changes in the Fear of Recurrence Inventory Severity Subscale From Baseline to 13 Weeks | The Fear of Cancer Recurrence Inventory (FCRI; severity subscale) will be used to measure self-reported fear of recurrence. This 9-item subscale measures the presence and severity of the intrusive thoughts or images associated with the fear of cancer recurrence. Range is 0 to 36 with higher values representing higher fear of recurrence. | Baseline (Week 0), Week 13 | 
| Longitudinal Changes in the Health Status Questionnaire (SF-36) From Baseline to 13 Weeks | The Health Status Questionnaire (SF-36) functions as a self-reporting tool designed to evaluate an individual's quality of life. It consists of 36 items and is organized into eight subscales. Each subscale score is then translated into a linear scale that spans from 0 to 100. A higher score means enhanced quality of life. Additionally, the questionnaire incorporates two domains as mental health component and physical health component. These domains are the results of linear aggregation from the 8 subscales and transforming into T score metric. In these metrics, the t score has a mean of 50 and a standard deviation of 10 based on the characteristics of U.S. general population for both mental and physical health sub scores. A higher T-score corresponds to a higher quality of life for that subscale. | Baseline (Week 0), Week 13 | 
| Longitudinal Changes in the Impact of Events Scale-Revised (IES-R) From Baseline to 13 Weeks | The Impact of Events Scale - Revised (IES-R) is a 22-item self-report measure of cancer related distress. The IES-R assesses the frequency with which respondents experience intrusive thoughts, avoidant behaviors, and autonomic arousal specific to one's thoughts and feelings about cancer over the past week. Each item is rated on a 5-point scale ranging from 0(not at all) to 4(extremely). The higher grade indicates greater stress. IES- R total score is the sum of the means of the three subscale scores. IES- R total score ranges from 0 to 12. The higher scores indicate higher cancer distress. | Baseline (Week 0), Week 13 |