Folic Acid Clinical Trial for the Prevention of Cervical Cancer

The University of Alabama at Birmingham

Status and phase: Completed; Phase 2

Conditions: Precancerous Condition; Cervical Cancer

Treatments: Dietary Supplement: folic acid; Other: placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00703196

CDR0000579360

UAB-F060511015

UAB-IRB0000196

Details and patient eligibility

About

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.

Full 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.

Enrollment: 368 patients

Sex: Female

Ages: 19 to 120 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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368 participants in 2 patient groups, including a placebo group

Arm I

Experimental group

Description:

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

Treatment:

Dietary Supplement: folic acid

Arm II

Placebo Comparator group

Description:

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

Treatment:

Other: placebo