Chronic Kidney Disease Antidepressant Sertraline Trial

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized Trial of Sertraline Treatment of Depression in Chronic Kidney Disease

Conditions
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Chronic Kidney Disease, Depression

Intervention / Treatment
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* Drug: Sertraline
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sertraline<br>Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode | Drug: Sertraline<br>* Sertraline is a serotonin-selective reuptake inhibitor (SSRI) used to treat major depression. Dosage will begin at 50 mg/d and will be escalated by 50 mg increments every 2 weeks to a maximum of 200 mg/d<br>|
| Placebo Comparator: Placebo<br>Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode | Drug: placebo<br>* Placebo tablet will be identical and matched to sertraline tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Exit in Depression Symptom Severity as Measured by the QIDS-C-16 Score. | The score range is 0 to 27; higher scores indicate more severe depression; a score of 0 to 5 corresponds to a normal affect; 6 to 10 to a mild affect; 11 to 15 to a moderate affect; 16 to 20 to a severe affect; and 21 or greater to very severe depression. | baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | The score range is 0 to 27; higher scores indicate more severe depression; a score of 0 to 5 corresponds to a normal affect; 6 to 10 to a mild affect; 11 to 15 to a moderate affect; 16 to 20 to a severe affect; and 21 or greater to very severe depression. | baseline to 12 weeks | 
| Change From Baseline to Exit in Overall Function as Assessed by the Work and Social Adjustment Scale | Each item is rated on a 0 to 8 Likert scale with 0 indicating no impairment and 8 indicating severe impairment and a total score range of 0 to 40. | baseline to 12 weeks | 
| 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. | Raw scores from version 1.3 were transformed to a scale from 0 to 100, in which higher numbers signify more favorable quality of life. | baseline to 12 weeks | 
| Serious Adverse Events During the 12 Week Study Duration. | death, dialysis initiation, hospitalizations, or bleeding requiring transfusion | during 12 week study duration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Kidney Disease, Depression, Antidepressants, randomized controlled trial, treatment, Sertraline