Phase II Evaluation of AHCC for the Eradication of HPV Infections

Study Overview
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Brief Summary
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This is a phase II randomized, double-blind placebo-controlled, crossover trial. The primary outcome of this trial is achieving durable eradication persistent high risk HPV infection determined by HPV negative test results achieved while on active treatment with AHCC and maintained for 6 month post supplementation and 12 months post completion of AHCC treatment compared to placebo.

Detailed Description
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This is a phase II randomized, double-blind placebo-controlled, crossover trial. The primary outcome of this trial is achieving durable eradication HPV infection determined by HPV negative test results achieved while on active treatment with AHCC and maintained for 6 month post supplementation and 12 months post completion of AHCC treatment for Group 1. We will follow all patients for at least 12 months and up to 30 months depending on success of achieving a negative HPV testing results. After receiving AHCC 3 grams x 6 months if positive at the end of 12 months of study treatment, they are considered a treatment failure. If negative after completion of 6 months of AHCC supplementation + 6 months of placebo, they will continue on study for another six months (2 visits) to confirm they remain HPV negative and durable response. Group 2 will serve as untreated control for all time points (end of supplementation, then 6, 9, and 12 months post end of AHCC supplementation.

Official Title
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Phase II Randomized, Double-blind, Placebo-controlled Evaluation of AHCC (Active Hexose Correlated Compound) for the Eradication of HPV Infections in Women With HPV Positive Pap Smears

Conditions
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Human Papilloma Virus, Dysplasia, CIN1, CIN2

Intervention / Treatment
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* Dietary Supplement: AHCC 3 grams once a day
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Women over 30 years of age who have a HPV positive test and normal/negative cytology, atypical cells, ASCUS, or CIN1 or CIN2 cervical dysplasia within three months of study entry. Women must have had 2 other HPV positive tests with normal/negative cytology, atypical cells, ASCUS, or CIN1 or CIN2 cervical dysplasia 1 greater than 6 months and no more than 18 months prior to study entry 1 greater than 24 months prior to study entry. Women of child bearing potential must have a negative urine pregnancy test within 7 days of therapy start. Patients must have adequate hematologic, renal, and hepatic function as noted from labs within the previous 12 months: ANC >/= 1,500 cells/mm3, platelets 100,000 >/= cells/mm3; Creatinine clearance>/= 60 mL/min (estimated by Cockcroft Gault equation), total bilirubin, SGPT, SGOT, and alkaline phosphatase </= 1.5 times normal. Patients of child-bearing age must agree to use effective methods of contraception (oral contraceptives, condoms, etc.) while on study. Exclusion Criteria: • History of myocardial infarction within past 6 months, unstable angina, CHF, or uncontrolled hypertension (> 140/90). Women with a current or prior diagnosis of cancer Women with a current diagnosis of CIN3 cervical dysplasia Women that are pregnant or breast feeding. Women with a history of Hepatitis (autoimmune, A, B, or C) or antigen positive Patients with history of significant psychiatric disorders (schizophrenia, bipolar, psychosis) or uncontrolled seizures. Patients with significant medical co-morbidities at the discretion of the primary Gynecologist. Including immunosuppressive conditions (i.e. HIV+, rheumatoid arthritis, etc) or taking immune modulation mediations (i.e. immunosuppressants) Women that have taken AHCC within the past six months. Women currently taking other immune modulating nutritional supplements. Patients who have undergone a hysterectomy (supracervical hysterectomy allowed)

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, double-blind, placebo control phase II study that patients receive either AHCC or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>AHCC 3 grams once a day on an empty stomach x 6 months then placebo once a day x 56 months. | Dietary Supplement: AHCC 3 grams once a day<br>* AHCC supplementation x 6 months with Placebo x 6 months<br>* Other names: active hexose correlated compound;|
| Placebo Comparator: Group 2<br>Placebo once a day on an empty stomach x 12 months | Other: Placebo<br>* Placebo supplementation x 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Roche, COBAS HPV DNA Assay (Pleasanton, CA) | HPV DNA testing | once every 3 months for 12 months up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Interferon beta | Evaluation of Interferon Beta level | once every 3 months for 12 months up to 18 months | 
| Interferon gamma | Evaluation of Interferon gamma level | once every 3 months for 12 months up to 18 months | 
| NK Cells | Evaluation of Natural Killer (NK) cells | once every 3 months for 12 months up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, AHCC, nutritional supplement