Sertraline Compared With Hypericum Perforatum (St.John's Wort) in Treating Depression

Condition(s) targeted: Depression; Unspecified Adult Solid Tumor, Protocol Specific

Intervention: Zoloft 50 mg (Drug); St. John's Wort 600 mg (Dietary Supplement)

Phase: Phase 3

Status: Completed

Sponsored by: Wake Forest NCORP Research Base

Official(s) and/or principal investigator(s):
Antonius A. Miller, MD, Principal Investigator, Affiliation: Comprehensive Cancer Center of Wake Forest University
Edward G. Shaw, MD, Study Chair, Affiliation: Comprehensive Cancer Center of Wake Forest University

RATIONALE: Antidepressants such as sertraline and the herb hypericum perforatum (St. John's wort) may be effective in treating mild to moderate depression. It is not yet known which treatment is more effective in improving depression in patients who have cancer. PURPOSE: This randomized phase III trial is studying how well sertraline works compared to St. John's wort in treating mild to moderate depression in patients with solid tumors.

Official title: A Phase III Double-Blind Randomized Trial Comparing Sertraline (Zoloft) And Hypericum Perforatum (St. John's Wort) In Cancer Patients With Mild To Moderate Depression

Study design: Allocation: Randomized, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Supportive Care

Primary outcome: Compare the change in depression severity as measured by Hamilton Depression rating scale at 4 months

Secondary outcome:

Compare the severity of somnolence, nausea, and insomnia

Compare Impact of Sertraline and St. John's wort on fatigue

Correlate the hyperforin concentrations with the change in depression severity

Detailed description: OBJECTIVES:

- Compare the change in depression severity in cancer patients with mild to moderate

depression treated with sertraline vs Hypericum perforatum.

- Compare the severity of somnolence, nausea, and insomnia in patients treated with these

regimens.

- Compare the impact of these regimens on fatigue in these patients.

- Correlate hyperforin concentrations with change in depression severity in patients

treated with Hypericum perforatum. OUTLINE: This is a randomized, double-blind study. Patients are stratified according to level of depression (mild vs moderate), concurrent radiotherapy (yes vs no), and TNM stage (I, II, or III vs IV). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients receive oral sertraline daily.

- Arm II: Patients receive oral Hypericum perforatum daily. In both arms, treatment

continues for 4 months in the absence of unacceptable toxicity. Measurements of depression, somnolence, nausea, insomnia, fatigue, and hyperforin concentration are assessed at baseline, and at 1, 2, and 4 months. PROJECTED ACCRUAL: A maximum of 250 patients will be accrued for this study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

INCLUSION CRITERIA:

- Mild or moderate depression as determined by the following criteria (see Section 7. 1

and 8. 0)

- Mild : HRSD score 10-14; moderate: HRSD score 15-19 (Appendix IV)

- At least 2 of nine symptoms of depression on the PHQ (Appendix V)

- At least one of the nine PHQ symptoms must be either depressed/irritable mood or

anhedonia

- Histologically or cytologically documented solid tumor, lymphoma, or primary or

metastatic brain tumor > 6 months from radiation with stable disease or no evidence of disease.

- Concurrent cancer chemotherapy with sertraline or St. John's wort is not allowed,

therefore patients must have no plan for chemotherapy for 4 months

- Prior chemotherapy is allowed, but patients must be >4 weeks from prior chemotherapy

except >6 weeks from prior mitomycin-C or nitrosourea

- Patients receiving Rituxin, Herceptin, Erbitux, Interferon, etc. are eligibile for

this study while under treatment.

- Prior or concurrent radiation is allowed except brain irradiation for brain

metastases or primary brain tumor. Must be > 6 months from radiation with stable disease or no evidence of disease.

- Age > 18 years

- ECOG performance status 0 -1 (Appendix III)

- Life expectancy >4 months

- Required initial laboratory values (within 3 days of registration): hemoglobin >10

g/dl and bilirubin <1. 5 mg/dl, negative pregnancy test

- Signed protocol specific informed consent prior to registration

- Patient recruitment this study will be done through the out patient clinic. The

research PI or designee including clinic physician, resident, research nurse or research assistant will review medical information to determine or verify protocol eligibility either at the time the patient is being seen in the clinic for a routine visit/consult or prior to the patient's clinic visit. EXCLUSION CRITERIA:

- A patient will be excluded if he/she is (a) judged to be severely depressed using the

following criteria: HRSD score 20 or more or a positive score on PHQ item i (suicidal ideation) or (b) judged not to be depressed by a score of 9 or less on the HRSD or fewer than two PHQ items scored positively. A patient who is found to be severely depressed or suicidal, either on initial screening or during the trial will be referred for appropriate treatment.

- Psychotic symptoms, dementia, marked agitation requiring medication

- Current or previous alcohol or drug dependence

- Hematologic malignancy (i. e., leukemias, multiple myeloma)

- Planned chemotherapy in the next 4 months

- Antidepressant or St. John's wort use in the last 4 weeks

- Current or planned use of erythropoietin (Procrit®, Aranesp®)

- Current or planned use of theophylline, warfarin (except for central line

prophylaxis), protease inhibitors used to treat AIDS, digoxin, cyclosporin, benzodiazepines (such as diazepam, alprazolam, etc), calcium-channel blockers (such as diltiazem, nifedipine, etc), coenzyme A reductase inhibitors (cholesterol lowering agents), macrolide antibiotics (such as azithromycin, erythromycin, clarithromycin, etc), griseofulvin, phenobarbital, phenytoin, rifampin, rifabutin, ketoconazole, fluconazole, itraconazole, corticosteroids, grapefruit juice, or other naturopathic/herbal products that could interfere with St. John's wort (call study chairman with questions).

- Pregnant or nursing women

Bay Area Tumor Institute, Oakland, California 94609-3305, United States

Regional Radiation Oncology Center at Rome, Rome, Georgia 30165, United States

CCOP - Central Illinois, Decatur, Illinois 62526, United States

CCOP - Southeast Cancer Control Consortium, Goldsboro, North Carolina 27534-9479, United States

High Point Regional Hospital, High Point, North Carolina 27261, United States

Comprehensive Cancer Center at Wake Forest University, Winston-Salem, North Carolina 27157-1082, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: March 2004
Last updated: April 3, 2013