Chronic Kidney Disease Antidepressant Sertraline Trial

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

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Sertraline
  • 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
• Drug: placebo
  • Placebo tablet will be identical and matched to sertraline tablet.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode
• Placebo Comparator: 2
  • Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode

Primary Measures

• Improvement in depression symptom severity as measured by the QIDS-C-16 score.
  • Time Frame: 12 weeks
    Safety Issue?: No

Secondary Measures

• 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
  • Time Frame: 12 weeks
    Safety Issue?: No
• Improvement in overall function as assessed by the Work and Social Adjustment Scale
  • Time Frame: 12 weeks
    Safety Issue?: No
• Improvement in quality of life
  • Time Frame: 12 weeks
    Safety Issue?: No
• Serious adverse events
  • Time Frame: 12 weeks
    Safety Issue?: Yes
• Reduction in platelet aggregation and activation in sertraline vs. placebo group, and whether this reduction correlates with higher plasma sertraline levels.
  • Time Frame: 12 weeks
    Safety Issue?: Yes
• Determine if sertraline treatment vs. placebo will improve: a. nutritional status; b. adherence to prescribed medications; c. cognitive functioning; and d. markers of inflammation.
  • Time Frame: 12 weeks
    Safety Issue?: No

Inclusion Criteria:

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

Exclusion Criteria:

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 21 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Department of Veterans Affairs U.S. Fed

Overall Clinical Trial Officials and Contacts

Susan Hedayati, MD MHS Principal Investigator VA North Texas Health Care System, Dallas  

Overall Contact: Susan Hedayati, MD MHS (214) 857-2214 susan.hedayati@va.gov

Information obtained from ClinicalTrials.gov on February 02, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00946998

Study ID Number: CLIN-008-09S

ClinicalTrials.gov Identifier: NCT00946998

Health Authority: United States: Federal Government