A Trial of Sertraline vs. CBT for End-stage Renal Disease Patients With Depression {ASCEND}

NCT ID: NCT02358343

Last Updated: 2019-07-23

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

184 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-23

Study Completion Date

2017-12-15

Brief Summary

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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

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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.

Conditions

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Depression End Stage Renal Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Engagement Interview

Subjects will be randomly assigned to engagement interview or a control visit.Trained CBT therapists at each of the three sites will conduct the engagement interview. The session will be aimed at improving the acceptance of the diagnosis of depression by patients and treatment for the same.

Group Type ACTIVE_COMPARATOR

Engagement Interview

Intervention Type BEHAVIORAL

An Engagement Interview will comprise a one-on-one session with the patient, during which the health-care provider will use reflective statements and non-judgmental listening techniques, will explore barriers to treatment, and will help patient articulate ambivalence about engaging in treatment. This session will be enhanced with a 40-minute DVD that the subject will watch with the therapist in the dialysis facility. The subject will be encouraged to take the DVD home with them and watch it with their family members as well.

Control Visit

Subjects will be randomly assigned to engagement interview or a control visit. Individuals assigned to control visit will be scheduled for a follow-up discussion with a member of the research team. During this session, they will be informed of the diagnosis of major depression or dysthymia, the options for treatment available through the clinical trial, and alternatives should they decline participation in the clinical trial.

Group Type NO_INTERVENTION

No interventions assigned to this group

Cognitive Behavioral Therapy

The subjects will be randomly assigned to individual CBT or sertraline drug therapy using block randomization.

Individuals will undergo 10 CBT sessions of 60 minutes each, by a trained therapist in the dialysis facility (8 weekly sessions; then every other week x 2). The CBT will be administered while the patient is undergoing HD; however, alternative arrangements will be made upon individual patient's preferences.

Group Type ACTIVE_COMPARATOR

Cognitive Behavioral Therapy

Intervention Type BEHAVIORAL

Cognitive Behavioral Therapy (CBT) is a short-term psychotherapy that will focus on how the individual is thinking, behaving, and communicating today rather than on their childhood experience. The therapist will assist the patient in identifying specific distortions (cognitive assessment) and biases in thinking and will provide guidance on how to change this thinking. During the course of intervention, study subjects will undergo assessment of severity of depressive symptoms using Quick Inventory of Depressive Symptoms - Self-Report (QIDS-SR) every two weeks for the first six weeks (weeks 0, 2, 4, and 6) and every three weeks for the next six weeks (weeks 9 and 12).

Antidepressant Drug Therapy

The subjects will be randomly assigned to individual CBT or sertraline drug therapy using block randomization. Anti-Depressant Drug Therapy will be delivered with sertraline, a selective serotonin reuptake inhibitor, and the dose will be titrated using the Measurement Based Care Protocol.

Group Type ACTIVE_COMPARATOR

Antidepressant Drug Therapy

Intervention Type DRUG

The site investigators will prescribe sertraline drug at a starting dose of 25 mg oral tablets. Dose titration will be implemented using standardized assessments of depressive symptoms and drug side effects; and the research team and the patient make joint decisions to maintain, increase, or decrease the dose. This will help establish the highest effective but tolerable dose tailored for each patient. The QIDS-SR scale will be used to assess the clinical response for dose titration. The FIBSER scale will be used to assess side effects and the degree to which they interfere with day-to-day functions. The participant-specific dose at week 6, up to a maximum of 200 mg/d, will be continued for the remaining 6 weeks.

Observational Cohort

Subjects who (1) are not willing to participate in the clinical trial and (2) do not find any treatment acceptable outside the clinical trial will be invited to participate in the prospective observational cohort for serial assessment of depressive symptoms.These subjects will only undergo assessment of severity of depressive symptoms at weeks 0, 6, and 12 using QIDS-C.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Engagement Interview

An Engagement Interview will comprise a one-on-one session with the patient, during which the health-care provider will use reflective statements and non-judgmental listening techniques, will explore barriers to treatment, and will help patient articulate ambivalence about engaging in treatment. This session will be enhanced with a 40-minute DVD that the subject will watch with the therapist in the dialysis facility. The subject will be encouraged to take the DVD home with them and watch it with their family members as well.

Intervention Type BEHAVIORAL

Cognitive Behavioral Therapy

Cognitive Behavioral Therapy (CBT) is a short-term psychotherapy that will focus on how the individual is thinking, behaving, and communicating today rather than on their childhood experience. The therapist will assist the patient in identifying specific distortions (cognitive assessment) and biases in thinking and will provide guidance on how to change this thinking. During the course of intervention, study subjects will undergo assessment of severity of depressive symptoms using Quick Inventory of Depressive Symptoms - Self-Report (QIDS-SR) every two weeks for the first six weeks (weeks 0, 2, 4, and 6) and every three weeks for the next six weeks (weeks 9 and 12).

Intervention Type BEHAVIORAL

Antidepressant Drug Therapy

The site investigators will prescribe sertraline drug at a starting dose of 25 mg oral tablets. Dose titration will be implemented using standardized assessments of depressive symptoms and drug side effects; and the research team and the patient make joint decisions to maintain, increase, or decrease the dose. This will help establish the highest effective but tolerable dose tailored for each patient. The QIDS-SR scale will be used to assess the clinical response for dose titration. The FIBSER scale will be used to assess side effects and the degree to which they interfere with day-to-day functions. The participant-specific dose at week 6, up to a maximum of 200 mg/d, will be continued for the remaining 6 weeks.

Intervention Type DRUG

Other Intervention Names

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CBT Sertraline, "Zoloft"

Eligibility Criteria

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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.
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Texas

OTHER

Sponsor Role collaborator

University of New Mexico

OTHER

Sponsor Role collaborator

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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Rajnish Mehrotra

Professor of Medicine, Division of Nephrology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rajnish Mehrotra, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

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University of New Mexico

Albuquerque, New Mexico, United States

Site Status

University of Texas Southwestern

Dallas, Texas, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Hedayati SS, Bosworth HB, Kuchibhatla M, Kimmel PL, Szczech LA. The predictive value of self-report scales compared with physician diagnosis of depression in hemodialysis patients. Kidney Int. 2006 May;69(9):1662-8. doi: 10.1038/sj.ki.5000308.

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System, U.S.R.D., US Department of Public Health and Human Services, Public Health Service, National Institutes of Health, Bethesda, 2012.

Reference Type BACKGROUND

Glassman AH, O'Connor CM, Califf RM, Swedberg K, Schwartz P, Bigger JT Jr, Krishnan KR, van Zyl LT, Swenson JR, Finkel MS, Landau C, Shapiro PA, Pepine CJ, Mardekian J, Harrison WM, Barton D, Mclvor M; Sertraline Antidepressant Heart Attack Randomized Trial (SADHEART) Group. Sertraline treatment of major depression in patients with acute MI or unstable angina. JAMA. 2002 Aug 14;288(6):701-9. doi: 10.1001/jama.288.6.701.

Reference Type BACKGROUND
PMID: 12169073 (View on PubMed)

Cukor D, Rosenthal DS, Jindal RM, Brown CD, Kimmel PL. Depression is an important contributor to low medication adherence in hemodialyzed patients and transplant recipients. Kidney Int. 2009 Jun;75(11):1223-1229. doi: 10.1038/ki.2009.51. Epub 2009 Feb 25.

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Kutner NG, Zhang R, McClellan WM, Cole SA. Psychosocial predictors of non-compliance in haemodialysis and peritoneal dialysis patients. Nephrol Dial Transplant. 2002 Jan;17(1):93-9. doi: 10.1093/ndt/17.1.93.

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Reference Type BACKGROUND
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Reference Type DERIVED
PMID: 37651553 (View on PubMed)

Mehrotra R, Cukor D, Unruh M, Rue T, Heagerty P, Cohen SD, Dember LM, Diaz-Linhart Y, Dubovsky A, Greene T, Grote N, Kutner N, Trivedi MH, Quinn DK, Ver Halen N, Weisbord SD, Young BA, Kimmel PL, Hedayati SS. Comparative Efficacy of Therapies for Treatment of Depression for Patients Undergoing Maintenance Hemodialysis: A Randomized Clinical Trial. Ann Intern Med. 2019 Mar 19;170(6):369-379. doi: 10.7326/M18-2229. Epub 2019 Feb 26.

Reference Type DERIVED
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Reference Type DERIVED
PMID: 26621218 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://kri.washington.edu

Kidney Research Institute

Other Identifiers

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48647

Identifier Type: -

Identifier Source: org_study_id

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