Folic Acid Clinical Trial for the Prevention of Cervical Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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HPV Clearance by Folic Acid Supplementation (FACT for HPV)

Conditions
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Cervical Cancer, Precancerous Condition

Intervention / Treatment
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* Dietary Supplement: folic acid
* Other: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>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<br>* Given orally once daily<br>|
| Placebo Comparator: Arm II<br>Patients receive oral placebo once daily for 12 months in the absence of unacceptable toxicity or any other adverse effects. | Other: placebo<br>* Given orally once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clearance of HPV 16 and other coexisting HR-HPV and incidence of CIN ≥ 2 |  | One Year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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