Diindolylmethane in Treating Patients With Abnormal Cervical Cells

Cervical Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00462813
• Other study ID #: CRUK-CRISP-1
• Secondary ID: CDR0000539352ISR
• Status: Completed
• Phase: Phase 3
• First received: April 18, 2007
• Last updated: August 6, 2013
• Start date: October 2004
• Est. completion date: January 2010

Study information

• Verified date: September 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 3000
• Est. completion date: January 2010
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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)

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cervical Cancer
• Precancerous Condition
• Precancerous Conditions
• Uterine Cervical Neoplasms

Intervention

Drug:
• oral microencapsulated diindolylmethane

Genetic:
• polymerase chain reaction

Other:
• cervical Papanicolaou test

• cytology specimen collection procedure

Procedure:
• colposcopic biopsy

Locations

Country	Name	City	State
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Barts and the London School of Medicine	London	England

Sponsors (1)

Lead Sponsor	Collaborator
Barts and the London School of Medicine and Dentistry

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Biopsy confirmed high-grade cervical intraepithelial neoplasia (CIN) at 6 months			No
Secondary	Change in lesion size at 6 months			No
Secondary	Human papillomavirus (HPV) status and characteristics (type, viral load, and integration) at baseline and 6 months			No
Secondary	Change in cervical cytology at 6 months			No
Secondary	CIN = grade 3 on histology at 6 months			No
Secondary	Long term follow-up (i.e., 7 years)			No
Secondary	Migraine, premenstrual syndrome (PMS), menstruation, and body weight			No

External Links

•   Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial. Br J Cancer. 2012 Jan 3;106(1):45-52. doi: 10.1038/bjc.2011.496. Epub 2011 Nov 10.