Clinical trial NCT04266275: Topical Curcumin for HPV Related Cervical Disease
Official title: An Investigation in the Use of Curcumin Topical Herbal Agent for the Treatment of Cervical Intraepithelial Neoplasia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Neoplasm Cervix
Keywords: Cancer
HIV
Oncology
Infectious disease
HPV
Preventive medicine
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2020-02-12
Enrollment: 200
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if curcumin can suppress HPV infection in women with low-grade squamous intraepithelial lesions (LSIL) disease or treated high-grade squamous intraepithelial lesions (HSIL) disease. This study plans to explore the effect of curcumin as a potential medical treatment in HIV-uninfected and infected women with mild precancerous lesions of the cervix or recently treated high-grade precancerous lesions at risk for persistent HPV infection. About 200 women with low-grade precancerous lesions of the cervix or recently treated high-grade precancerous lesions will be enrolled to either insert 2000 mg of curcumin capsules in their vagina once a week or placebo after undergoing colposcopy or loop electrosurgical excision procedure (LEEP). They will have a repeat visit in 6 months where they will undergo a Pap smear and HPV test to determine if there are higher rates of HPV clearance after curcumin administration. If HPV is present or the Pap smear is abnormal, patients will then undergo colposcopic examination to evaluate cervical histology.

Detailed description: Cervical cancer is the third most common cancer worldwide. The causative agent responsible for cervical cancer is the persistent infection with oncogenic Human Papillomavirus (HPV). Rates of cervical cancer and HPV infection are increased particularly in HIV-infected women due to immunosuppression with cervical cancer categorized as an AIDS-defining diagnosis. Despite the promise of HPV vaccine in the prevention of cervical cancer, the widespread availability of this vaccine is limited due to cost and accessibility. Therefore, prevention strategies to reduce the risk of cervical cancer after HPV exposure entail treatment at the premalignant state, including low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL), along with the eradication of HPV infection. There is a desperate need for an inexpensive, non-invasive alternative method to treat these premalignant cervical lesions and potentially suppress HPV infection.

Curcumin, an extract from turmeric, a popular culinary spice, has been used in traditional Indian medicine for its anti-inflammatory and anti-infectious properties. Recent studies have shown the potential effect of curcumin to reduce tumors and precancerous lesions in animal and human cancer cells. It is postulated that curcumin achieves its effect on cancer cells by modulating different cellular pathways as well as altering HPV effect on tissue cells.

The purpose of this study is to see if curcumin can suppress HPV infection in women with LSIL disease or treated HSIL disease. The researchers plan to explore the effect of curcumin as a potential medical treatment in HIV-uninfected and infected women with mild precancerous lesions of the cervix or recently treated high-grade precancerous lesions at risk for persistent HPV infection. About 200 women with low-grade precancerous lesions of the cervix or recently treated high-grade precancerous lesions will be enrolled to either insert 2000 mg of curcumin capsules in their vagina once a week or placebo after undergoing colposcopy or LEEP. They will have a repeat visit in 6 months where they will undergo a Pap smear and HPV test to determine if there are higher rates of HPV clearance after curcumin administration. If HPV is present or the Pap smear is abnormal, patients will then undergo colposcopic examination to evaluate cervical histology.

Eligibility criteria: Inclusion Criteria:

* HIV-uninfected and infected women (without current AIDS-defining illness)
* Presence of a cervix
* Biopsy-proven LSIL disease or recently treated HSIL disease
* Adherence to combined anti-retrovirals (cART) if HIV infected
* On continuous antiretrovirals with a cluster of differentiation 4 (CD4) count \>200 cells/ml with sustained undetectable viral load for at least 3 months (only for HIV-positive participants)
* On reliable birth control: combined oral contraceptive pills (OCP), long-acting reversible contraception (LARC), bilateral tubal ligation (BTL) or Depo-Provera (birth control shot)
* Willing to conform to the study requirements
* Reliable follow-up and contact information
* No risk factors for HSIL or microinvasive disease (no colposcopic features of microinvasion, adequate colposcopy and negative endocervical curettage)
* For women with HSIL only, LEEP completed within 6 weeks preceding initial encounter with study staff and adequate wound healing

Exclusion Criteria:

* Untreated HSIL or invasive features on colposcopy and the biopsy specimen
* Not adherent to anti-retroviral therapy (cART) (HIV infected participants)
* CD4 count =\<200 cells/ml and detectable viral load within the last 3 months (only for HIV-positive participants)
* Lactating and pregnant people
* Patient with irregular cycles (more than once a month)
* Not on reliable birth control.
* Previous hysterectomy
* Prior diagnosis of cervical cancer, treated or untreated
* Inability to provide informed consent
* Medical condition that interferes with the conduct of the study in the investigator's opinion
* Evidence of active cervical infection or serious cervical disease necessitating surgery
* Known bleeding diathesis

Primary outcomes:
measure: HPV Clearance
timeFrame: Month 6
Secondary outcomes:
measure: Disease Recurrence
timeFrame: Month 6
Other outcomes:
measure: Participant Discontinuation
timeFrame: Month 6
Locations:
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Grady Hospital - Ponce De Leon Clinic
state: Georgia
Study officials:
affiliation: Emory University
name: Lisa Flowers, MD
role: PRINCIPAL_INVESTIGATOR
References: