Diindolylmethane in Treating Patients With Abnormal Cervical Cells

Sponsor

Barts and the London School of Medicine and Dentistry (Other)

Overall Status

Completed

CT.gov ID

NCT00462813

Collaborator

(none)

3,000

Enrollment

Locations

Duration (Months)

1500

Patients Per Site

23.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of diindolylmethane, a substance found in cruciferous vegetables, may keep cervical intraepithelial neoplasia or cervical cancer from forming.

PURPOSE: This randomized phase III trial is studying diindolylmethane to see how well it works compared to a placebo in treating patients with abnormal cervical cells.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer Precancerous Condition	Drug: oral microencapsulated diindolylmethane Genetic: polymerase chain reaction Other: cervical Papanicolaou test Other: cytology specimen collection procedure Procedure: colposcopic biopsy	Phase 3

Detailed Description

OBJECTIVES:

Compare the effect of diindolylmethane vs placebo in reducing the prevalence of histologically proven high-grade cervical intraepithelial neoplasia in patients with low-grade cervical cytological abnormalities.
Compare the effect of these regimens in reducing the prevalence of cytological abnormalities in these patients.
Compare the effect of these regimens in changing the clinical appearance of the cervix in these patients.
Determine if diindolylmethane offers benefits in relation to human papillomavirus (HPV) status, including HPV type, viral load, and integration.
Determine the side effects of supplementation with diindolylmethane.
Determine the effects of this drug on migraine, mastalgia, weight, and premenstrual syndrome (PMS).

OUTLINE: This is a double-blind, randomized, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral diindolylmethane once daily for 6 months.
Arm II: Patients receive oral placebo once daily for 6 months. Patients undergo cervical sampling at baseline and at 6 months for Pap testing by liquid based cytology and human papillomavirus (HPV) testing by polymerase chain reaction. Some patients also undergo urine and hair sample collection at baseline and at 3 and 6 months. Samples are analyzed for estrogen and diindolylmethane metabolites, to monitor patient compliance and response to treatment. Some patients have a cervical photograph taken using a colposcope at baseline and at 6 months. All patients undergo colposcopy at 6 months.

Patients complete a questionnaire at baseline (i.e., for reproductive history, diet, smoking, and premenstrual symptoms) and at 6 months (i.e., for side effects, compliance, changes in smoking, and contraception use). Patients with moderate to severe premenstrual syndrome (PMS) also complete PMS questionnaires once monthly during months 1-6 and 4 months following completion of study therapy. All patients are instructed to maintain current diet and to keep cruciferous vegetables and soy products constant during study course.

After completion of study treatment, patients are followed periodically for up to 7 years.

PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

3000 participants

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Prevention

Official Title:

An Investigation Into the Effects of Diidolylmethane (BioResponse DIM®) Supplementation in Women With Low-Grade Cervical Cytological Abnormalities [CRISP-1]

Study Start Date :

Oct 1, 2004

Actual Primary Completion Date :

Jun 1, 2008

Actual Study Completion Date :

Jan 1, 2010

Outcome Measures

Primary Outcome Measures

Biopsy confirmed high-grade cervical intraepithelial neoplasia (CIN) at 6 months []

Secondary Outcome Measures

Change in lesion size at 6 months []
Human papillomavirus (HPV) status and characteristics (type, viral load, and integration) at baseline and 6 months []
Change in cervical cytology at 6 months []
CIN ≥ grade 3 on histology at 6 months []
Long term follow-up (i.e., 7 years) []
Migraine, premenstrual syndrome (PMS), menstruation, and body weight []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

First mildly dyskaryotic Pap smear or a second borderline Pap smear taken within the Cervical Screening Wales program
Patients under surveillance following treatment for high-grade cervical intraepithelial neoplasia are not eligible
No clinical suspicion of a concurrent invasive cervical cancer

PATIENT CHARACTERISTICS:

No invasive cancer within the past 3 years
No known HIV positivity
Not pregnant or nursing
Not planning to become pregnant within the next 6 months

PRIOR CONCURRENT THERAPY:

No concurrent immunosuppressive drugs, warfarin, or theophylline
No concurrent proton pump inhibitor drugs for ulcer or reflux disease (i.e., rabeprazole, esomeprazole magnesium, lansoprazole, omeprazole, or pantoprazole sodium)