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

Sponsor

Wake Forest University Health Sciences (Other)

Overall Status

Completed

CT.gov ID

NCT00066859

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arms

Duration (Months)

0.3

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Depression Unspecified Adult Solid Tumor, Protocol Specific	Drug: Zoloft 50 mg Dietary Supplement: St. John's Wort 600 mg	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Supportive Care

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 Start Date :

Mar 1, 2004

Actual Primary Completion Date :

Apr 1, 2005

Actual Study Completion Date :

Nov 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1: Sertraline (Zoloft) 50 mg Zoloft 50 mg by mouth daily for 1 week if tolerated dose may be increased to 100 mg daily for 4 months	Drug: Zoloft 50 mg Zoloft 50 mg by mouth daily for 1 week if tolerated dose may be increased to 100 mg daily for 4 months Other Names: Sertraline Zoloft
Active Comparator: Arm 2 - St. John's Wort 600mg St. John's wort 600 mg daily for 1 week. If tolerated dose may be increased to 900 mg daily for four months.	Dietary Supplement: St. John's Wort 600 mg St. John's wort 600 mg daily for 1 week, if tolerated. Dose may be increased to 900 mg daily for 4 months. Other Names: Hypericum perforatum

Arm

Intervention/Treatment

Active Comparator: Arm 1: Sertraline (Zoloft) 50 mg

Zoloft 50 mg by mouth daily for 1 week if tolerated dose may be increased to 100 mg daily for 4 months

Drug: Zoloft 50 mg

Zoloft 50 mg by mouth daily for 1 week if tolerated dose may be increased to 100 mg daily for 4 months

Other Names:

Sertraline

Zoloft

Active Comparator: Arm 2 - St. John's Wort 600mg

St. John's wort 600 mg daily for 1 week. If tolerated dose may be increased to 900 mg daily for four months.

Dietary Supplement: St. John's Wort 600 mg

St. John's wort 600 mg daily for 1 week, if tolerated. Dose may be increased to 900 mg daily for 4 months.

Other Names:

Hypericum perforatum

Outcome Measures

Primary Outcome Measures

Depression severity as measured by Hamilton Depression rating scale. [4 months]
To compare the change in depression severity in cancer patients with mild to moderate depression on sertraline and St. John's wort.

Secondary Outcome Measures

Somnolence, nausea, and insomnia as assessed by the NCI Common Toxicity Criteria. The Epworth Sleepiness Scale will also be used to assess somnolence. [4 months]
Fatigue as measured by the Functional Assessment of Chronic Illness Therapy-Fatigue Scale. [4 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bay Area Tumor Institute	Oakland	California	United States	94609-3305
2	Regional Radiation Oncology Center at Rome	Rome	Georgia	United States	30165
3	CCOP - Central Illinois	Decatur	Illinois	United States	62526
4	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina	United States	27534-9479
5	High Point Regional Hospital	High Point	North Carolina	United States	27261
6	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082

Sponsors and Collaborators

Wake Forest University Health Sciences
National Cancer Institute (NCI)

Investigators

Principal Investigator: Antonius A. Miller, MD, Wake Forest University Health Sciences
Study Chair: Edward G. Shaw, MD, Wake Forest University Health Sciences