Chronic Kidney Disease Antidepressant Sertraline Trial (CAST)
Primary Purpose
Chronic Kidney Disease, Depression
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Sertraline
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Kidney Disease focused on measuring Chronic Kidney Disease, Depression, Antidepressants, randomized controlled trial, treatment, Sertraline
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
Sites / Locations
- VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
- University of Texas Southwestern Medical Center at Dallas
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Sertraline
Placebo
Arm Description
Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode
Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode
Outcomes
Primary Outcome Measures
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.
Secondary Outcome 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
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.
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.
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.
Serious Adverse Events During the 12 Week Study Duration.
death, dialysis initiation, hospitalizations, or bleeding requiring transfusion
Full Information
NCT ID
NCT00946998
First Posted
July 23, 2009
Last Updated
February 9, 2018
Sponsor
VA Office of Research and Development
Collaborators
University of Texas Southwestern Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1. Study Identification
Unique Protocol Identification Number
NCT00946998
Brief Title
Chronic Kidney Disease Antidepressant Sertraline Trial
Acronym
CAST
Official Title
Randomized Trial of Sertraline Treatment of Depression in Chronic Kidney Disease
Study Type
Interventional
2. Study Status
Record Verification Date
February 2018
Overall Recruitment Status
Completed
Study Start Date
February 8, 2010 (Actual)
Primary Completion Date
November 23, 2016 (Actual)
Study Completion Date
November 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VA Office of Research and Development
Collaborators
University of Texas Southwestern Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Disease, Depression
Keywords
Chronic Kidney Disease, Depression, Antidepressants, randomized controlled trial, treatment, Sertraline
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
201 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Sertraline
Arm Type
Active Comparator
Arm Description
Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode
Intervention Type
Drug
Intervention Name(s)
Sertraline
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Placebo tablet will be identical and matched to sertraline tablet.
Primary Outcome Measure Information:
Title
Change From Baseline to Exit in Depression Symptom Severity as Measured by the QIDS-C-16 Score.
Description
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.
Time Frame
baseline to 12 weeks
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
baseline to 12 weeks
Title
Change From Baseline to Exit in Overall Function as Assessed by the Work and Social Adjustment Scale
Description
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.
Time Frame
baseline to 12 weeks
Title
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.
Description
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.
Time Frame
baseline to 12 weeks
Title
Serious Adverse Events During the 12 Week Study Duration.
Description
death, dialysis initiation, hospitalizations, or bleeding requiring transfusion
Time Frame
during 12 week study duration
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan S Hedayati, MD MHS
Organizational Affiliation
University of Texas Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
City
Dallas
State/Province
Texas
ZIP/Postal Code
75216
Country
United States
Facility Name
University of Texas Southwestern Medical Center at Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
23085503
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.
Results Reference
result
PubMed Identifier
29101402
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.
Results Reference
result
PubMed Identifier
35368605
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.
Results Reference
derived
PubMed Identifier
31664940
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.
Results Reference
derived
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Chronic Kidney Disease Antidepressant Sertraline Trial
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