Folic Acid Clinical Trial for the Prevention of Cervical Cancer

Sponsor

University of Alabama at Birmingham (Other)

Overall Status

Completed

CT.gov ID

NCT00703196

Collaborator

National Cancer Institute (NCI) (NIH)

368

Enrollment

Location

Arms

Study Details

Study Description

Brief Summary

RATIONALE: Supplements, such as folic acid, may stop or delay the development of cervical cancer in women infected with human papillomavirus.

PURPOSE: This phase II trial is studying how well folic acid supplements work in preventing cancer in women infected with human papillomavirus.

Condition or Disease	Intervention/Treatment	Phase
Cervical Cancer Precancerous Condition	Dietary Supplement: folic acid Other: placebo	Phase 2

Detailed Description

OBJECTIVES:

Primary

Evaluate the effects of folic acid supplementation on clearance of human papilloma virus (HPV) 16 and other specific types of HR-HPV and on prevention of the progression of ≤ cervical intraepithelial neoplasia (CIN) 1 lesions (not true preneoplastic lesions) to CIN ≥ 2 (true neoplastic lesions) by conducting a 12-month double-blind randomized placebo-controlled trial with 5 mg of folic acid/day.

Secondary

Evaluate whether the clearance of HPV 16 and other specific HR-HPV types and the progression of cervical lesions (≤ CIN 1 to CIN ≥ 2) is modified by lower levels of circulating and/or cervical cell folate, presence of micronuclei or global DNA hypomethylation in cervical cells, presence of integrated vs episomal HPV 16, or a high HPV 16 viral load in cervical cells at the enrollment.

OUTLINE: This is a single center study. Patients are stratified according to multivitamin use (yes vs no) and smoking status (smoker vs nonsmoker). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral folic acid pill once daily for 12 months in the absence of unacceptable toxicity or any other adverse effects.
Arm II: Patients receive oral placebo once daily for 12 months in the absence of unacceptable toxicity or any other adverse effects.

All patients complete a diet, physical activity, and a risk factor questionnaire at the enrollment visit (0-month) and at 4, 8, and 12 month visits (a total of 4 visits). Fasting blood samples for assessing circulating concentrations of micronutrients (folate, vitamins B12, A, E, C, and total carotenes) and exfoliated cervical cell samples for assessing HPV are collected at all 4 visits. Anthropometric measures are taken at all study visits. A colposcopically directed biopsy is taken at the 0-month visit and at the 12-month visit to assess the histological diagnoses of cervical lesions.

Study Design

Study Type:

Interventional

Actual Enrollment :

368 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Prevention

Official Title:

HPV Clearance by Folic Acid Supplementation (FACT for HPV)

Study Start Date :

Mar 1, 2007

Actual Primary Completion Date :

May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral folic acid pill once daily for 12 months in the absence of unacceptable toxicity or any other adverse effects.	Dietary Supplement: folic acid Given orally once daily
Placebo Comparator: Arm II Patients receive oral placebo once daily for 12 months in the absence of unacceptable toxicity or any other adverse effects.	Other: placebo Given orally once daily

Arm

Intervention/Treatment

Experimental: Arm I

Patients receive oral folic acid pill once daily for 12 months in the absence of unacceptable toxicity or any other adverse effects.

Dietary Supplement: folic acid

Given orally once daily

Placebo Comparator: Arm II

Patients receive oral placebo once daily for 12 months in the absence of unacceptable toxicity or any other adverse effects.

Other: placebo

Given orally once daily

Outcome Measures

Primary Outcome Measures

Clearance of HPV 16 and other coexisting HR-HPV and incidence of CIN ≥ 2 [One Year]

Eligibility Criteria

Criteria

Ages Eligible for Study:

19 Years to 120 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Received care at the Health Departments in Alabama and with an abnormal pap result, including any of the following:
Atypical squamous cells of undetermined significance (ASCUS)
ASCUS, cannot exclude high-grade lesion (ASCUS-H)
Low-grade squamous intraepithelial lesion
High-grade squamous intraepithelial lesion
Referred to University of Alabama at Birmingham (UAB) Highlands Clinic for further colposcopic examination by Ob/Gyn physicians
Tested positive for human papilloma virus (HPV) 16 and diagnosed with ≤ cervical intraepithelial neoplasia (CIN) 1 lesions at the 0-month visit
With or without concurrent infections with other HR (High Risk) HPV types (HPV 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68)
Not diagnosed with true preneoplastic lesions of the cervix based on a colposcopically directed biopsy

PATIENT CHARACTERISTICS:

Not pregnant
Willing to take study pills, keep scheduled follow-up study visits, or communicate with study personnel about changes in contact information during the study period
No prior diagnosis or treatment for colon polyps or breast lumps

PRIOR CONCURRENT THERAPY:

No prior treatment for cervical cancer or precancerous condition
No prior surgeries involving the cervix
No concurrent antifolate medications such as methotrexate, sulfasalazine or phenytoin
No concurrent or planned consumption of 400 μg or more of a folic acid supplement on a regular basis
Not involved in any other clinical trial