Combination of Novel Therapies for CKD Comorbid Depression
키워드
요약
기술
Aim 1. Compare the efficacy and tolerability of two 16-week strategies vs. control for treatment of CKD patients with MDD starting with (1) BAT or (2) bupropion, each augmented to a combination of both in non-remitters. Primary hypothesis: Treatment with either strategy will improve depression (primary endpoint) and be tolerable.
Patients with non-dialysis stages 3b-5 CKD and MDD (N=201) will be randomized 1:1:1 to 16 weeks of:
Strategy 1: Single-blind BAT plus placebo, augmented in non-remitters at 8 weeks with single-blind bupropion; Strategy 2: Double-blind bupropion plus single-blind Clinical Management (CM) attention control, augmented in non-remitters at 8 weeks with single-blind BAT; Control: CM attention control plus placebo. There will be >80% power to detect a minimal clinically important difference (MCID) of 2 points on the Quick Inventory of Depressive Symptomatology between each intervention and control, assuming a 14% attrition rate.
Exploratory aim (a): Explore if remote access to therapy via internet vs. travel to clinic affects treatment efficacy.
Aim 2. Investigate efficacy and tolerability of 8 weeks (Phase 1) of (1) BAT plus placebo or (2) bupropion plus CM, vs. control, for improvement in depression. Secondary hypothesis: Treatment with 8 weeks of BAT or bupropion will improve depression. There will be 80% power to detect a MCID of 2 points between each arm and control, assuming 10% attrition.
Exploratory aims:
(a) Investigate whether patient preference for BAT vs. drug affects treatment efficacy; (b) compare efficacy of each combination in Phase 2 with control; (c) compare change from baseline in plasma C-reactive protein in drug vs. BAT or control arms.
Aim 3. Investigate the efficacy of these two 16-week treatment strategies vs. control for improvement in CKD patient-centered outcomes including: (a) adherence to medications and healthcare visits; (b) fatigue; (c) sleep; (d) overall functioning. Secondary hypothesis: Treatment with either strategy will result in clinically meaningful improvements in adherence, fatigue, sleep and overall functioning in patients with CKD.
날짜
| 마지막 확인: | 05/31/2020 |
| 처음 제출: | 06/04/2020 |
| 제출 된 예상 등록: | 06/07/2020 |
| 처음 게시 됨: | 06/08/2020 |
| 제출 된 마지막 업데이트: | 06/08/2020 |
| 마지막 업데이트 게시: | 06/10/2020 |
| 실제 연구 시작 날짜: | 07/31/2020 |
| 예상 기본 완료 날짜: | 03/31/2025 |
| 예상 연구 완료 날짜: | 03/31/2026 |
상태 또는 질병
개입 / 치료
Drug: Strategy 2
Behavioral: Strategy 1
Drug: Placebo
Other: Clinical Management
단계
팔 그룹
| 팔 | 개입 / 치료 |
|---|---|
| Active Comparator: Strategy 1 Strategy 1: Single-blind Behavioral Activation Therapy plus placebo for 8 weeks (Phase 1), augmented in non-remitters at 8 weeks with single-blind bupropion (Phase 2) for another 8 weeks. | Behavioral: Strategy 1 Brief behavioral activation treatments administered via video tele-conferencing. |
| Active Comparator: Strategy 2 Strategy 2: Double-blind bupropion plus single-blind Clinical Management (CM) attention control for 8 weeks (Phase 1), augmented in non-remitters at 8 weeks with single-blind BAT (Phase 2) for another 8 weeks. | Drug: Strategy 2 Bupropion is an anti-depressant medication. |
| Placebo Comparator: Control Control: Clinical management attention control plus placebo for 16 weeks |
자격 기준
| 공부할 수있는 연령 | 18 Years 에 18 Years |
| 공부할 수있는 성별 | All |
| 건강한 자원 봉사자를 받아들입니다 | 예 |
| 기준 | Inclusion Criteria: 1. Male or female adults aged 18 years or greater. There will be no upper age limit. 2. Presence of CKD stages 3b, 4 or non-dialysis stage 5, with an estimated glomerular filtration rate (GFR) of <45 mL/min/1.73 m2 for a period of at least 3 months, as defined by the National Kidney Foundation and determined using the four-variable Modification of Diet for Renal Diseases Study formula. 3. Presence of a current Major Depressive Disorder (MDD) based on MINI DSM IV-based criteria 4. Quick Inventory of Depressive Symptomatology-Self-report (QIDS-SR) score of ≥11 at enrollment and ≥11 on QIDS-Clinician Rated (QIDS-C) at randomization. 5. Able to understand and sign informed consent after the nature of the study has been fully explained Exclusion Criteria: 1. Unable to understand or give informed consent. 2. Unwilling or unable to participate in the protocol or comply with any of its components 3. Receiving chronic dialysis 4. Kidney transplant recipient 5. Significant hepatic dysfunction or liver enzyme abnormalities 3 times or greater than the upper limit of normal 6. Terminal chronic obstructive pulmonary disease or cancer 7. Presence of seizure disorder 8. Current use of class I anti-arrhythmic medications (such as 1C propafenone and flecanide), pimozide, MAO inhibitors, reserpine, guanethidine, cimetidine, or methyldopa; tri-cyclic anti-depressants, neuroleptics, or anti-convulsants 9. Use of serotonergic drugs or supplements such as triptans, tramadol, linezolid, tryptophan, and St. John's Wort. 10. Use of medications known to cause QT prolongation on EKG 11. Ongoing use of antidepressant medications for depression treatment 12. Past treatment failure on bupropion 13. Initiation of depression-focused psychotherapy in the 3 months prior to study entry 14. Active 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 <23 17. Active suicidal intent 18. Pregnancy, lactation, or women of childbearing potential not willing to use adequate contraception |
결과
1 차 결과 측정
1. Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C) [Assessed at baseline and weeks 4, 6, 8, 12, and 16]
2 차 결과 측정
1. Serious adverse events [Assessed at weeks 4, 6, 8, 12, and 16.]
2. Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C) [Assessed at baseline and weeks 4, 6, and 8.]
3. Serious adverse events with monotherapy [Assessed at weeks 4, 6, and 8.]
4. Quick Inventory of Depressive Symptomatology-Clinician Rated scale (QIDS-C) [Assessed at weeks 8, 12, and 16.]
5. High sensitivity C-reactive protein [Assessed at baseline and week 8]
6. Adherence to medications by Pill Count [Assessed at weeks 4, 8, 12, and 16.]
7. Fatigue assessed by the Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scale [Assessed at baseline and weeks 4, 8, 12, and 16]
8. Sleep assessed by the Insomnia Severity Index (ISI) [Assessed at baseline and weeks 4, 8, 12, and 16]
9. Overall functioning assessed by the Sheehan Disability Scale (SDS) [Assessed at baseline and weeks 4, 8, 12, and 16]
