Clinical trial NCT00946998: Chronic Kidney Disease Antidepressant Sertraline Trial
Official title: Randomized Trial of Sertraline Treatment of Depression in Chronic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Kidney Disease
Depression
Keywords: Chronic Kidney Disease
Depression
Antidepressants
randomized controlled trial
treatment
Sertraline
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: University of Texas Southwestern Medical Center
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2009-07-27
Enrollment: 201
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: This is a randomized double-blinded placebo-controlled trial to see if treatment with sertraline as compared with placebo tablets will improve depression symptoms in patients with chronic kidney disease who have not yet started dialysis or received a kidney transplant. The investigators will also investigate whether sertraline treatment will improve quality of life and whether it is safe to use in patients with kidney disease. The study subject will be randomly assigned to take either sertraline or a placebo tablet for 12 weeks.

Detailed description: This is a randomized double-blinded placebo-controlled trial of adults with predialysis stages 3-5 Chronic Kidney Disease and Major Depressive Episode. Subjects will be randomized in a double-blind fashion to placebo or sertraline (beginning at 50 mg/d and escalated by 50 mg increments every 2 weeks to a maximum of 200 mg/d) and followed for 12 weeks. The primary outcome is to investigate if treatment with sertraline, as compared with placebo, results in an improvement in depression symptom severity as measured by the Quick Inventory of Depressive Symptomatology Clinician Rated (QIDS-C-16) score. Secondary outcomes include whether sertraline, as compared with placebo, improves overall function and quality of life and whether it will result in more serious adverse events.

Eligibility criteria: Inclusion Criteria:

* Male or female adults aged greater than 21 years.
* Predialysis stages 3, 4 or 5 CKD.
* Current Major Depressive Episode.
* QID-C-16 score of 11.
* Able to understand and sign informed consent.

Exclusion Criteria:

* No healthcare power of attorney to sign informed consent.
* Unwilling or unable to participate.
* Kidney transplant recipient.
* Initiated on maintenance dialysis
* Significant hepatic dysfunction or liver enzyme abnormalities 3 times the upper limits of normal.
* Terminal chronic obstructive pulmonary disease or cancer.
* Recent history of active bleeding, such as gastrointestinal bleeding requiring hospitalization 3 months prior
* Current use of class I anti-arrhythmic medications.
* Use of pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine or methyldopa; tri-cyclic anti-depressants, neuroleptics or anti-convulsants, excluding gabapentin
* Use of other serotonergic drugs or supplements such as triptans, tramadol, linezolid, tryptophan, and St. John's Wort.
* Ongoing use of anti-depressants
* Past treatment failure on Sertraline
* Initiation of psychotherapy for depression in the 3 months prior to study entry
* Alcohol or substance abuse or dependence that requires acute detoxification at study entry
* Present or past psychosis or Bipolar I or II disorder
* Dementia or a Mini-Mental State Examination score of \<23
* Suicidal ideation
* Pregnancy, lactation and women of childbearing potential not using adequate contraception

Primary outcomes:
measure: Change From Baseline to Exit in Depression Symptom Severity as Measured by the QIDS-C-16 Score.
timeFrame: baseline to 12 weeks
Secondary outcomes:
measure: Response to Treatment Defined as a Decline of 50% in the Baseline QIDS-C-16 Score and Remission of Depression Defined as a QIDS-C-16 Score of 5
timeFrame: baseline to 12 weeks
measure: Change From Baseline to Exit in Overall Function as Assessed by the Work and Social Adjustment Scale
timeFrame: baseline to 12 weeks
measure: Change in Quality of Life From Baseline to Exit in the Kidney Disease Quality of Life -Short Form, Version 1.3, Patient-reported Overall Health.
timeFrame: baseline to 12 weeks
measure: Serious Adverse Events During the 12 Week Study Duration.
timeFrame: during 12 week study duration
Other outcomes:
Locations:
city: Dallas
country: United States
facility: VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center at Dallas
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Susan S Hedayati, MD MHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jain N, Trivedi MH, Rush AJ, Carmody T, Kurian B, Toto RD, Sarode R, Hedayati SS. Rationale and design of the Chronic Kidney Disease Antidepressant Sertraline Trial (CAST). Contemp Clin Trials. 2013 Jan;34(1):136-44. doi: 10.1016/j.cct.2012.10.004. Epub 2012 Oct 22.
citation: Hedayati SS, Gregg LP, Carmody T, Jain N, Toups M, Rush AJ, Toto RD, Trivedi MH. Effect of Sertraline on Depressive Symptoms in Patients With Chronic Kidney Disease Without Dialysis Dependence: The CAST Randomized Clinical Trial. JAMA. 2017 Nov 21;318(19):1876-1890. doi: 10.1001/jama.2017.17131.
citation: Gregg LP, Carmody T, Le D, Bharadwaj N, Trivedi MH, Hedayati SS. Depression and the Effect of Sertraline on Inflammatory Biomarkers in Patients with Nondialysis CKD. Kidney360. 2020 Apr 13;1(6):436-446. doi: 10.34067/KID.0000062020. eCollection 2020 Jun 25.
citation: Jain N, Wan F, Kothari M, Adelodun A, Ware J, Sarode R, Hedayati SS. Association of platelet function with depression and its treatment with sertraline in patients with chronic kidney disease: analysis of a randomized trial. BMC Nephrol. 2019 Oct 29;20(1):395. doi: 10.1186/s12882-019-1576-7.