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

Depression Clinical Trial

— ASCEND  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02358343
• Other study ID #: 48647
• Status: Completed
• Phase: Phase 3
• Start date: March 23, 2015
• Est. completion date: December 15, 2017

Study information

• Verified date: July 2019
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: December 15, 2017
• Est. primary completion date: November 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• End Stage Renal Disease
• Kidney Diseases
• Kidney Failure, Chronic

Intervention

Behavioral:
• 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.
• 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).

Drug:
• 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.

Locations

Country	Name	City	State
United States	University of New Mexico	Albuquerque	New Mexico
United States	University of Texas Southwestern	Dallas	Texas
United States	University of Washington	Seattle	Washington

Sponsors (4)

Lead Sponsor	Collaborator
University of Washington	Patient-Centered Outcomes Research Institute, University of New Mexico, University of Texas

Country where clinical trial is conducted

United States, 

References & Publications (17)

Atalay H, Solak Y, Biyik M, Biyik Z, Yeksan M, Uguz F, Guney I, Tonbul HZ, Turk S. Sertraline treatment is associated with an improvement in depression and health-related quality of life in chronic peritoneal dialysis patients. Int Urol Nephrol. 2010 Jun;42(2):527-36. doi: 10.1007/s11255-009-9686-y. Epub 2009 Dec 2. — View Citation

Cukor D, Coplan J, Brown C, Peterson RA, Kimmel PL. Course of depression and anxiety diagnosis in patients treated with hemodialysis: a 16-month follow-up. Clin J Am Soc Nephrol. 2008 Nov;3(6):1752-8. doi: 10.2215/CJN.01120308. Epub 2008 Aug 6. — View Citation

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. — View Citation

Cukor D, Ver Halen N, Asher DR, Coplan JD, Weedon J, Wyka KE, Saggi SJ, Kimmel PL. Psychosocial intervention improves depression, quality of life, and fluid adherence in hemodialysis. J Am Soc Nephrol. 2014 Jan;25(1):196-206. doi: 10.1681/ASN.2012111134. Epub 2013 Oct 10. — View Citation

Davison SN, Jhangri GS. The impact of chronic pain on depression, sleep, and the desire to withdraw from dialysis in hemodialysis patients. J Pain Symptom Manage. 2005 Nov;30(5):465-73. — View Citation

Duarte PS, Miyazaki MC, Blay SL, Sesso R. Cognitive-behavioral group therapy is an effective treatment for major depression in hemodialysis patients. Kidney Int. 2009 Aug;76(4):414-21. doi: 10.1038/ki.2009.156. Epub 2009 May 20. — View Citation

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. Erratum in: JAMA 2002 Oct 9;288(14):1720. — View Citation

Hedayati SS, Bosworth HB, Briley LP, Sloane RJ, Pieper CF, Kimmel PL, Szczech LA. Death or hospitalization of patients on chronic hemodialysis is associated with a physician-based diagnosis of depression. Kidney Int. 2008 Oct;74(7):930-6. doi: 10.1038/ki.2008.311. Epub 2008 Jun 25. — View Citation

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. — View Citation

Hedayati SS, Minhajuddin AT, Toto RD, Morris DW, Rush AJ. Validation of depression screening scales in patients with CKD. Am J Kidney Dis. 2009 Sep;54(3):433-9. doi: 10.1053/j.ajkd.2009.03.016. Epub 2009 Jun 3. — View Citation

Kimmel PL, Peterson RA, Weihs KL, Simmens SJ, Alleyne S, Cruz I, Veis JH. Multiple measurements of depression predict mortality in a longitudinal study of chronic hemodialysis outpatients. Kidney Int. 2000 May;57(5):2093-8. — View Citation

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. — View Citation

Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, Markowitz JC, Ninan PT, Kornstein S, Manber R, Thase ME, Kocsis JH, Keller MB. The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. 2003 Sep 1;54(5):573-83. Erratum in: Biol Psychiatry. 2003 Sep 1;54(5):585. — View Citation

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

Weisbord SD, Fried LF, Arnold RM, Fine MJ, Levenson DJ, Peterson RA, Switzer GE. Prevalence, severity, and importance of physical and emotional symptoms in chronic hemodialysis patients. J Am Soc Nephrol. 2005 Aug;16(8):2487-94. Epub 2005 Jun 23. — View Citation

Weisbord SD, Fried LF, Mor MK, Resnick AL, Unruh ML, Palevsky PM, Levenson DJ, Cooksey SH, Fine MJ, Kimmel PL, Arnold RM. Renal provider recognition of symptoms in patients on maintenance hemodialysis. Clin J Am Soc Nephrol. 2007 Sep;2(5):960-7. Epub 2007 Aug 8. — View Citation

Wisniewski SR, Rush AJ, Balasubramani GK, Trivedi MH, Nierenberg AA; STARD Investigators. Self-rated global measure of the frequency, intensity, and burden of side effects. J Psychiatr Pract. 2006 Mar;12(2):71-9. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Initiated Depression Treatment	The primary measure of efficacy of the Engagement Interview will be the number of patients undergoing hemodialysis with co-morbid depression who initiate treatment for the condition.; This will be defined as one of the following: Completing at least one psychotherapy session either as a part of the clinical trial or in the community within four weeks of establishing a diagnosis of major depression and/or dysthymia.; Receiving a supply of anti-depressant drug either as a part of the clinical trial or the treating physician within four weeks of establishing a diagnosis of major depression and/or dysthymia.	within four weeks of engagement interview or control visit
Primary	QIDS-C Score	The Quick Inventory of Depressive Symptomatology Clinician-rated (QIDS-C) scale ranges from 0-27, higher scores indicate worse depression. The primary measure of efficacy of Intervention will be the mean difference in QIDS-C score at Week 12 between treatment groups.	Week 12 of treatment
Secondary	Number of Participants Who Accepted Depression Treatment	The secondary measure of efficacy of the Engagement Interview will be the % of patients undergoing hemodialysis with co-morbid depression who are willing to accept treatment.; This will be measured by the patient's intent and will be defined as one of the following: Signing the informed consent to be randomly assigned to individual CBT or drug therapy; Receiving a referral by the research team and/or primary care physician and/or treating nephrologist to a therapist for psychotherapy in the community.; Receiving a prescription for anti-depressant drug therapy from primary care physician and/or treating nephrologist within two weeks of establishing a diagnosis of major depression/dysthymia.	within two weeks of engagement interview or control visit
Secondary	BDI-II	Beck Depression Inventory-II, range 0-63, higher scores indicate worse depression	Week 12
Secondary	GAD-7	Generalized Anxiety Disorder 7-item Scale, range 0-21, higher scores indicate worse anxiety	Week 12
Secondary	Sheehan Disability Scale	range 0-30, higher scores indicate worse disability	Week 12
Secondary	SF-36 Energy/Vitality	Energy/vitality subscale of the 36-Item Short Form Health Survey, range 0-100, higher scores indicate better energy/vitality	Week 12
Secondary	Global Quality of Life Scale	range 0-10, higher scores indicate better quality of life	Week 12
Secondary	Satisfaction With Life Scale	range 1-35, higher scores indicate better satisfaction	Week 12
Secondary	Perceived Social Support	Multi-Dimensional Scale of Perceived Social Support, range 1-7, higher scores indicate better social support	Week 12
Secondary	PSQI	Pittsburgh Sleep Quality Index, range 0-21, higher scores indicate worse sleep quality	Week 12
Secondary	Exercise	Single item activity measure, range 1-6, higher indicates less activity	Week 12
Secondary	Percentage of Dialysis Treatment Sessions Skipped and/or Shortened	Treatment Adherence with Dialysis as defined by the percentage of all dialysis sessions skipped and/or requested by the patient to be shortened by = 10 minutes over the 12-week intervention period. Dialysis sessions missed due to hospitalization will not be included as a skipped treatment.	Over 12 Weeks
Secondary	Percent Inter-dialytic Weight Gain	Treatment Adherence with Fluid Intake as defined by inter-dialytic weight gain (as % of post-dialysis weight) during Week 12 of the study	Week 12
Secondary	Serum Phosphorus Level	Treatment Adherence with Diet and/or Medications as defined by Serum phosphorus level measured as a part of routine clinical care during the third month of participation in the study.	Week 12

External Links

•   ASCEND Trial Website
•   Kidney Research Institute