Clinical trial NCT02358343: A Trial of Sertraline vs. CBT for End-stage Renal Disease Patients With Depression {ASCEND}
Official title: ASCEND: A Trial of Sertraline vs. CBT for End-stage Renal Disease Patients With Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Depression
End Stage Renal Disease
Keywords: Comorbid Depression
Major Depressive Disorder
Dysthymia
Cognitive Behavioral therapy (CBT)
Sertraline
Engagement Interview
End Stage Renal Disease (ESRD)
Hemodialysis
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: University of Texas
name: University of New Mexico
name: Patient-Centered Outcomes Research Institute
First posted: 2015-02-06
Enrollment: 184
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Patients whose kidneys fail generally require dialysis treatments to sustain life. The ability of patients to make major adjustments in their lives for dialysis is hampered by depression that affects almost one-quarter of such individuals. There are no studies that have adequately tested whether treatment of depression is effective in dialysis patients and if there is any difference between the response to the two most commonly available forms of treatment, psychotherapy and anti-depressant drug therapy.

To fill this important gap in the investigators knowledge, the investigators propose to undertake (1) a randomized controlled clinical trial of 200 patients to test whether an engagement interview will result in a higher proportion of dialysis patients accepting treatment for depression; and (2) a randomized controlled clinical trial of 120 patients to determine whether there is any difference in the likelihood of improvement of depressive symptoms with psychotherapy or drug therapy among dialysis patients with depression. Patients in these studies will be enrolled from among individuals receiving care in 50 dialysis facilities in three metropolitan areas - Seattle, Dallas, and Albuquerque. The research proposal has been developed with the support of patients, caregivers, and stakeholders to ensure that the findings from the study are relevant to them and can be readily implemented in day-to-day clinical practice. Hence, the engagement interview and psychotherapy will be delivered in a dialysis facility to ease the burden on patients, and the dose of the study drug will be changed in partnership with the study participants. In addition to depressive symptoms, the effect of treatment on other meaningful outcomes such as fatigue and sleep will be determined.

The two forms of treatment for depression being tested in this clinical trial are very different from each other and patients differ with regards to the treatment option preferable and/or available to them. Successful completion of the clinical trial will provide patients, caregivers, and other stakeholders with the information that they would need when faced with a diagnosis of depression in patients undergoing hemodialysis. This will allow patients to select evidence-based treatments to improve outcomes that are relevant to them.

Detailed description: BACKGROUND Patients with end-stage renal disease undergoing maintenance hemodialysis (HD) have to adjust to complex treatment regimens, and experience frequent care transitions. This is compounded by a four-fold higher prevalence of comorbid depression than in the general population, which is strongly associated with poor patient-centered outcomes. Yet, depression is often not diagnosed when present, not treated when identified, and many HD patients are reluctant to accept treatment. This is likely a result of lack of high-quality evidence for the efficacy of different treatment options for comorbid depression in HD patients. OBJECTIVES Conduct an open-label, randomized controlled clinical trial among HD patients with comorbid depression to (1) compare the efficacy of an engagement interview with usual care in increasing acceptability of treatment (n=200); and (2) compare the efficacy of 12 weeks of cognitive behavioral therapy (CBT) or anti-depressant drug therapy (sertraline) for reducing the severity of depressive symptoms, and other meaningful outcomes (n=120). METHODS HD patients in up to 50 dialysis facilities in three different regions (Albuquerque, NM; Dallas, TX; Seattle, WA) will be pre-screened for the presence of clinically significant depressive symptoms. Patients with a confirmed diagnosis of major depression or dysthymia will be randomly assigned to an engagement interview or usual care to determine efficacy in increasing acceptability of treatment (n=200). Individuals who agree to treatment will be randomly assigned to individual CBT or drug therapy. CBT will be administered in a dialysis facility by a trained therapist. Sertraline will be titrated to the maximum tolerated dose using Measurement Based Care, a model of shared-decision-making. Patient-reported outcomes will be measured by a single assessor for all three sites, blinded to the treatment assignment. The primary efficacy measure will be a change in severity of depressive symptoms; secondary outcome measures will assess other important patient-reported outcomes such as somatic symptom burden, functioning, and adherence with dialysis treatment, diet, and medications. The longitudinal evolution of symptoms in patients who refuse to accept any treatment either within or outside the clinical trial will also be studied (n=40). PATIENT OUTCOMES (PROJECTED) This study will provide answers to three questions faced by HD patients with clinically significant depressive symptoms: (1) "Given my preferences, what should I expect will happen to me?"; (2) "What are my options, and what are the potential benefits and harms of these options?"; and (3) "What can I do to improve the outcomes that are most important to me?" Oversight of study will be provided by separate Patient Council and Stakeholder Council to align with PCORI's mission of generating high-integrity, evidence-based information from research guided by patients, caregivers, and broader health care community.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 21 years;
2. Undergoing thrice-weekly maintenance HD for ≥ 3 months;
3. Able to speak either English or Spanish;
4. BDI-II score ≥ 15; and
5. Meets diagnostic criteria for either current major depressive episode or dysthymia on the MINI.

Exclusion Criteria:

1. Active suicidal intent;
2. Ongoing psychotherapy or current treatment with certain anti-depressant drugs;
3. Evidence of cognitive impairment on Mini-Cog;
4. Present or past psychosis or bipolar disorder I or II on the MINI;
5. Alcohol or substance abuse diagnosed on the MINI or history of such abuse in the past three months;
6. Life expectancy \< 3 months, in the judgment of the site principal investigator;
7. Anticipated to receive living related donor kidney transplantation within 3 months;
8. Pregnancy, or lactation, or women of childbearing age not willing to use adequate birth control;
9. Clinical and/or laboratory evidence of chronic liver disease;
10. History of significant active bleeding in the past three months, such as hospitalization for gastrointestinal bleeding;
11. Current use of class I anti-arrhythmic medications (e.g., propafenone, flecainide), pimozide, monoamine oxidase inhibitors, reserpine, guanethidine, cimetidine, tri-cyclic anti-depressants, triptans, tramadol, linezolid, tryptophan, and St. John's wort; and
12. Known hypersensitivity to sertraline.

Primary outcomes:
measure: Number of Participants Who Initiated Depression Treatment
timeFrame: within four weeks of engagement interview or control visit
measure: QIDS-C Score
timeFrame: Week 12 of treatment
Secondary outcomes:
measure: Number of Participants Who Accepted Depression Treatment
timeFrame: within two weeks of engagement interview or control visit
measure: BDI-II
timeFrame: Week 12
measure: GAD-7
timeFrame: Week 12
measure: Sheehan Disability Scale
timeFrame: Week 12
measure: SF-36 Energy/Vitality
timeFrame: Week 12
measure: Global Quality of Life Scale
timeFrame: Week 12
measure: Satisfaction With Life Scale
timeFrame: Week 12
measure: Perceived Social Support
timeFrame: Week 12
measure: PSQI
timeFrame: Week 12
measure: Exercise
timeFrame: Week 12
measure: Percentage of Dialysis Treatment Sessions Skipped and/or Shortened
timeFrame: Over 12 Weeks
measure: Percent Inter-dialytic Weight Gain
timeFrame: Week 12
measure: Serum Phosphorus Level
timeFrame: Week 12
Other outcomes:
Locations:
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Dallas
country: United States
facility: University of Texas Southwestern
state: Texas
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Rajnish Mehrotra, MD
role: PRINCIPAL_INVESTIGATOR
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