Chronic Kidney Disease, Depression
Conditions
Keywords
Chronic Kidney Disease, Depression, Antidepressants, randomized controlled trial, treatment, Sertraline
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.
Interventions
DRUGSertraline
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
DRUGplacebo
Placebo tablet will be identical and matched to sertraline tablet.
Sponsors
University of Texas Southwestern Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Exit in Depression Symptom Severity as Measured by the QIDS-C-16 Score. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | baseline to 12 weeks | 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. | baseline to 12 weeks | 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. | during 12 week study duration | death, dialysis initiation, hospitalizations, or bleeding requiring transfusion |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sertraline Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode
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 | 97 |
| Placebo Patients with predialysis Chronic Kidney Disease stages 3-5 and with major depressive episode
placebo: Placebo tablet will be identical and matched to sertraline tablet. | 96 |
| Total | 193 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Exited prior to first outcome assessment | 5 | 3 |
Baseline characteristics
| Characteristic | Total | Placebo | Sertraline |
|---|---|---|---|
| 16-item Quick Inventory of Depression Symptomatology Clinician-rated Score | 14.0 units on a scale STANDARD_DEVIATION 2.4 | 14.1 units on a scale STANDARD_DEVIATION 2.4 | 14.0 units on a scale STANDARD_DEVIATION 2.4 |
| Age, Continuous | 58.4 years STANDARD_DEVIATION 13.4 | 59.1 years STANDARD_DEVIATION 12.2 | 57.7 years STANDARD_DEVIATION 14.5 |
| Chronic Kidney Disease Stage CKD Stage 3 | 90 Participants | 44 Participants | 46 Participants |
| Chronic Kidney Disease Stage CKD Stage 4 | 70 Participants | 36 Participants | 34 Participants |
| Chronic Kidney Disease Stage CKD Stage 5 | 33 Participants | 16 Participants | 17 Participants |
| Diabetes Mellitus | 113 Participants | 55 Participants | 58 Participants |
| Estimated glomerular filtration rate | 27.5 mL/min/1.73 m^2 | 27.5 mL/min/1.73 m^2 | 27.0 mL/min/1.73 m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 14 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 158 Participants | 82 Participants | 76 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 111 Participants | 55 Participants | 56 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 81 Participants | 40 Participants | 41 Participants |
| Region of Enrollment United States | 193 participants | 96 participants | 97 participants |
| Sex: Female, Male Female | 52 Participants | 29 Participants | 23 Participants |
| Sex: Female, Male Male | 141 Participants | 67 Participants | 74 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 97 | 0 / 96 |
| other Total, other adverse events | 55 / 97 | 35 / 96 |
| serious Total, serious adverse events | 13 / 97 | 13 / 96 |
Outcome results
Primary
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.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sertraline | Change From Baseline to Exit in Depression Symptom Severity as Measured by the QIDS-C-16 Score. | -4.1 units on a scale |
| Placebo | Change From Baseline to Exit in Depression Symptom Severity as Measured by the QIDS-C-16 Score. | -4.2 units on a scale |
p-value: 0.82Mixed Models Analysis
Secondary
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.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sertraline | Change From Baseline to Exit in Overall Function as Assessed by the Work and Social Adjustment Scale | -5.0 units on a scale |
| Placebo | Change From Baseline to Exit in Overall Function as Assessed by the Work and Social Adjustment Scale | -3.2 units on a scale |
p-value: 0.32Mixed Models Analysis
Secondary
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.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sertraline | 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. | 0.0 units on a scale |
| Placebo | 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. | 0.0 units on a scale |
p-value: 0.61Mixed Models Analysis
Secondary
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.
Time frame: baseline to 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sertraline | 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 | Response (>/=50% decline in score) | 31 participants |
| Sertraline | 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 | Remission (score =/<5) | 15 participants |
| Placebo | 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 | Response (>/=50% decline in score) | 24 participants |
| Placebo | 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 | Remission (score =/<5) | 14 participants |
p-value: 0.28Mixed Models Analysis
p-value: 0.86Mixed Models Analysis
Secondary
Serious Adverse Events During the 12 Week Study Duration.
death, dialysis initiation, hospitalizations, or bleeding requiring transfusion
Time frame: during 12 week study duration
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sertraline | Serious Adverse Events During the 12 Week Study Duration. | Dialysis initiation | 7 Participants |
| Sertraline | Serious Adverse Events During the 12 Week Study Duration. | acute suicidal intent | 0 Participants |
| Sertraline | Serious Adverse Events During the 12 Week Study Duration. | Hospitalization other than dialysis initiation | 8 Participants |
| Sertraline | Serious Adverse Events During the 12 Week Study Duration. | bleed with transfusion or hospitalization | 2 Participants |
| Sertraline | Serious Adverse Events During the 12 Week Study Duration. | Death | 0 Participants |
| Placebo | Serious Adverse Events During the 12 Week Study Duration. | bleed with transfusion or hospitalization | 2 Participants |
| Placebo | Serious Adverse Events During the 12 Week Study Duration. | Death | 0 Participants |
| Placebo | Serious Adverse Events During the 12 Week Study Duration. | Dialysis initiation | 5 Participants |
| Placebo | Serious Adverse Events During the 12 Week Study Duration. | Hospitalization other than dialysis initiation | 7 Participants |
| Placebo | Serious Adverse Events During the 12 Week Study Duration. | acute suicidal intent | 1 Participants |
p-value: >0.99Chi-squared
p-value: 0.77Chi-squared
p-value: >0.99Chi-squared
p-value: 0.5Chi-squared
p-value: >0.99Chi-squared