Chronic Kidney DiseasePhase 3CASTNCT00946998
Chronic Kidney Disease Antidepressant Sertraline Trial
A Phase 3 study testing Sertraline in people with Chronic Kidney Disease and Depression, run by VA Office of Research and Development at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Chronic Kidney Disease, Depression
- What is being tested?
- Sertraline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 201 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Feb 2010to Nov 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 18Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
Dallas, Texas, 75216
University of Texas Southwestern Medical Center at Dallas
Dallas, Texas, 75390
About this study
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.
Read the 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.
- Conditions
- Chronic Kidney Disease, Depression
- Being tested
- Sertraline, placebo
- Keywords
- Chronic Kidney Disease, Depression, Antidepressants, randomized controlled trial, treatment, Sertraline
- Medical subject headings
- Renal Insufficiency, Chronic, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SertralineDrug
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
placeboDrug
Placebo tablet will be identical and matched to sertraline tablet.
| Study group | Role | What they receive |
|---|---|---|
| Sertraline | Active comparator | Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode Receives: Drug: Sertraline |
| Placebo | Placebo comparator | Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 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.
Measured: 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.
Measured: baseline to 12 weeks
Serious Adverse Events During the 12 Week Study Duration.
death, dialysis initiation, hospitalizations, or bleeding requiring transfusion
Measured: during 12 week study duration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2009 (estimated)
- Study start8 Feb 2010
- Primary completion23 Nov 2016
- Study completionNov 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 201 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Collaborators
- University of Texas Southwestern Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Responsible party
- Sponsor
- Investigators
- Susan S Hedayati, MD MHS, Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00946998
- Sponsor's protocol ID
- CLIN-008-09S
- Other IDs
- 1I01CX000217-01, 1R01DK085512-01A1
- Acronym
- CAST
- Status last verified
- Feb 2018
- First submitted
- 23 Jul 2009
- Last updated
- 9 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23085503Hedayati 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.
PubMed 29101402Gregg 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.
PubMed 35368605Jain 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.
PubMed 31664940
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Sertraline Treatment of Depression in Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT00946998
- Acronym / sponsor ID
- CAST / CLIN-008-09S
- Conditions
- Chronic Kidney Disease, Depression
- Keywords
- Chronic Kidney Disease, Depression, Antidepressants, randomized controlled trial, treatment, Sertraline
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 201 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Collaborators
- University of Texas Southwestern Medical Center, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 8 Feb 2010 (actual)
- Primary completion
- 23 Nov 2016 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 27 Jul 2009 (estimated)
- Results
- Posted 30 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sertraline | Active comparator | Drug: SertralinePatients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode |
| Placebo | Placebo comparator | Drug: placeboPatients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SertralineSertraline 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 | Sertraline |
| placeboPlacebo tablet will be identical and matched to sertraline tablet. | Drug | Placebo |
Primary outcome
Change From Baseline to Exit in Depression Symptom Severity as Measured by the QIDS-C-16 Score.
Time frame: baseline to 12 weeks
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.
4 secondary outcomes
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: baseline to 12 weeks
Change From Baseline to Exit in Overall Function as Assessed by the Work and Social Adjustment Scale
Time frame: 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.
Time frame: baseline to 12 weeks
Serious Adverse Events During the 12 Week Study Duration.
Time frame: during 12 week study duration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23085503Jain 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 publication: PubMed 29101402Hedayati 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.
- Derived from this study: PubMed 35368605Gregg 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.
- Derived from this study: PubMed 31664940Jain 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan S Hedayati, MD MHS principal investigator
University of Texas Southwestern Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sertraline in people with Chronic Kidney Disease and Depression, run by VA Office of Research and Development at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Exit in Depression Symptom Severity as Measured by the QIDS-C-16 Score. (time frame: baseline to 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00946998, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2018.