Folic Acid Clinical Trial for the Prevention of Cervical Cancer
Condition: Cervical Cancer; Precancerous Condition
MeSH terms: Uterine Cervical Neoplasms; Precancerous Conditions
Study type: Interventional
Phase: Phase 2

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.
    

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.
    

Intervention name(s): folic acid; placebo
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Given orally once daily; Given orally once daily
Intervention MeSH terms: Folic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: cervical cancer; human papilloma virus infection; low-grade squamous intraepithelial lesion; high-grade squamous intraepithelial lesion; atypical squamous cells of undetermined significance; cervical intraepithelial neoplasia grade 1; cervical intraepithelial neoplasia grade 2; cervical intraepithelial neoplasia grade 3