Clinical trial NCT00703196: Folic Acid Clinical Trial for the Prevention of Cervical Cancer
Official title: HPV Clearance by Folic Acid Supplementation (FACT for HPV)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cervical Cancer
Precancerous Condition
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
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-06-23
Enrollment: 368
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility 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

Primary outcomes:
measure: Clearance of HPV 16 and other coexisting HR-HPV and incidence of CIN ≥ 2
timeFrame: One Year
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Chandrika J. Piyathilake, PhD, MPH
role: STUDY_CHAIR
References: