Chronic Kidney Disease Antidepressant Sertraline Trial

NCT00946998 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: CLIN-008-09S1I01CX000217-011R01DK085512-01A1
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 2

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.

Conditions

Chronic Kidney Disease; Depression

Keywords

Chronic Kidney Disease; Depression; Antidepressants; randomized controlled trial; treatment; Sertraline

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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

  baseline to 12 weeks

• Change From Baseline to Exit in Overall Function as Assessed by the Work and Social Adjustment Scale

  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.

  baseline to 12 weeks

• Serious Adverse Events During the 12 Week Study Duration.

  during 12 week study duration

Study Arms (2)

Sertraline

ACTIVE COMPARATOR

Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode

Drug: Sertraline

Placebo

PLACEBO COMPARATOR

Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode

Drug: placebo

Interventions

Sertraline DRUG

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

Sertraline

placebo DRUG

Placebo tablet will be identical and matched to sertraline tablet.

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• VA Office of Research and Development: lead
• University of Texas Southwestern Medical Center: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX

Dallas, Texas, 75216, United States

Location

University of Texas Southwestern Medical Center at Dallas

Dallas, Texas, 75390, United States

Location

Related Publications (4)

• 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.

  PMID: 23085503 RESULT

• 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.

  PMID: 29101402 RESULT

• 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.

  PMID: 35368605 DERIVED

• 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.

  PMID: 31664940 DERIVED

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Depression

Interventions

Sertraline

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Susan Hedayati, MD, Professor of Medicine
• Organization: University of Texas Southwestern Medical Center

susan.hedayati@utsouthwestern.edu

214-645-6106

Study Officials

• Susan S Hedayati, MD MHS

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2009
• First Posted: July 27, 2009
• Study Start: February 8, 2010
• Primary Completion: November 23, 2016
• Study Completion: November 1, 2017
• Last Updated: March 9, 2018
• Results First Posted: January 30, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)