Topical Curcumin for HPV Related Cervical Disease

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ClinicalTrials.gov Identifier: NCT04266275

Recruitment Status : Not yet recruiting

First Posted : February 12, 2020

Last Update Posted : July 13, 2021

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

Lisa Flowers, Emory University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Neoplasm Cervix	Drug: Curcumin C3 Complex Drug: Placebo	Phase 2

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	200 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Care Provider, Investigator)
Primary Purpose:	Treatment
Official Title:	An Investigation in the Use of Curcumin Topical Herbal Agent for the Treatment of Cervical Intraepithelial Neoplasia
Estimated Study Start Date :	December 2021
Estimated Primary Completion Date :	December 31, 2022
Estimated Study Completion Date :	December 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Curcumin

Genetic and Rare Diseases Information Center resources: Cervical Intraepithelial Neoplasia

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Curcumin Arm Participants in this arm will use 2000 mg of intravaginal curcumin once a week for 20 weeks	Drug: Curcumin C3 Complex Curcumin (Curcumin C3 Complex prepared by Sabinsa Corporation), a constituent of the spice turmeric, is considered to be a low-toxicity, dietary-derived agent with chemopreventative and therapeutic benefits. Study participants will be instructed to insert four 500 mg (2000 mg total) curcumin capsules once a week (excluding days when they are on their menses) for 20 weeks. Participants will insert capsules using the vaginal applicator while lying on their back with their knees bent. Participants will be instructed to gently insert the capsules into the vagina as far as they will go comfortably, similar to a tampon insertion or other common intravaginal drugs. Cervical cytology and HPV testing will be performed at baseline and 6 months after the baseline visit. If cervical cytology or HPV testing is abnormal at 6 months, a colposcopy with biopsies will be performed. All samples will be used to analyze for the study outcomes.
Placebo Comparator: Placebo Arm Participants in this arm will use 2000 mg of intravaginal placebo once a week for 20 weeks	Drug: Placebo Study participants randomized to the placebo arm will insert four 500 mg (2000 mg total) of the placebo (gelatin) capsules once a week (excluding days when they are on their menses) for 20 weeks. Participants will insert the capsules using the vaginal applicator while lying on their back with their knees bent. Participants will be instructed to gently insert the capsules into the vagina as far as they will go comfortably, similar to a tampon insertion or other common intravaginal drugs. Cervical cytology and HPV testing will be performed at baseline and 6 months after the baseline visit. If cervical cytology or HPV testing is abnormal at 6 months, a colposcopy with biopsies will be performed. All samples will be used to analyze for the study outcomes.

Arm

Intervention/treatment

Experimental: Curcumin Arm

Participants in this arm will use 2000 mg of intravaginal curcumin once a week for 20 weeks

Drug: Curcumin C3 Complex

Curcumin (Curcumin C3 Complex prepared by Sabinsa Corporation), a constituent of the spice turmeric, is considered to be a low-toxicity, dietary-derived agent with chemopreventative and therapeutic benefits.

Study participants will be instructed to insert four 500 mg (2000 mg total) curcumin capsules once a week (excluding days when they are on their menses) for 20 weeks. Participants will insert capsules using the vaginal applicator while lying on their back with their knees bent. Participants will be instructed to gently insert the capsules into the vagina as far as they will go comfortably, similar to a tampon insertion or other common intravaginal drugs.

Cervical cytology and HPV testing will be performed at baseline and 6 months after the baseline visit. If cervical cytology or HPV testing is abnormal at 6 months, a colposcopy with biopsies will be performed. All samples will be used to analyze for the study outcomes.

Placebo Comparator: Placebo Arm

Participants in this arm will use 2000 mg of intravaginal placebo once a week for 20 weeks

Drug: Placebo

Study participants randomized to the placebo arm will insert four 500 mg (2000 mg total) of the placebo (gelatin) capsules once a week (excluding days when they are on their menses) for 20 weeks. Participants will insert the capsules using the vaginal applicator while lying on their back with their knees bent. Participants will be instructed to gently insert the capsules into the vagina as far as they will go comfortably, similar to a tampon insertion or other common intravaginal drugs.

Outcome Measures

Primary Outcome Measures :

HPV Clearance [ Time Frame: Month 6 ]
HPV clearance, assessed as the number of participants with undetectable high-risk HPV mRNA levels in the standard monolayer Pap test (ThinPrep), at 6 months will be compared between the curcumin and placebo study arms.

Secondary Outcome Measures :

Disease Recurrence [ Time Frame: Month 6 ]
Disease recurrence will be assessed either cytologic or histologic abnormality at 6 months. Rates of disease recurrence will be compared between study arms in HIV-uninfected and infected women.

Other Outcome Measures:

Participant Discontinuation [ Time Frame: Month 6 ]
The treatment will be considered tolerable if 25% or fewer of participants discontinue the study early.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	21 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04266275

Contacts

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Contact: Rachael Abraham, PhD	404-251-8940	rfaraha@emory.edu
Contact: Fletcher Neale	305-797-6397	michael.fletcher.neale.jr@emory.edu

Locations

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United States, Georgia
Emory University
Atlanta, Georgia, United States, 30303
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Contact: Fletcher Neale 305-797-6397 michael.fletcher.neale.jr@emory.edu
Contact: Rachael Abraham, PhD 404-251-8940 rfaraha@emory.edu
Principal Investigator: Lisa Flowers, MD
Grady Hospital - Ponce De Leon Clinic
Atlanta, Georgia, United States, 30308
Contact: Fletcher Neale 305-797-6397 michael.fletcher.neale.jr@emory.edu
Contact: Rachael Abraham, PhD 404-251-8940 rfaraha@emory.edu
Principal Investigator: Lisa Flowers, MD

Sponsors and Collaborators

Lisa Flowers

Investigators

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Principal Investigator:	Lisa Flowers, MD	Emory University

More Information

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Responsible Party:	Lisa Flowers, Professor, Emory University
ClinicalTrials.gov Identifier:	NCT04266275
Other Study ID Numbers:	STUDY00000758 IRB00117251 ( Other Identifier: Emory Previous IRB number )
First Posted:	February 12, 2020 Key Record Dates
Last Update Posted:	July 13, 2021
Last Verified:	July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Yes
Plan Description:	Individual participant data that underlie the published results will be made available for sharing after deidentification.
Supporting Materials:	Study Protocol Statistical Analysis Plan (SAP) Analytic Code
Time Frame:	Data will be available for sharing beginning 3 months and ending 5 years following article publication.
Access Criteria:	Data will be available for sharing with researchers providing a methodologically sound proposal, in order to achieve aims in the approved proposal. Proposals should be directed to lflowe2@emory.edu. To gain access, data requestor will need to sign a data access agreement.

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Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Lisa Flowers, Emory University:


Cancer HIV Oncology	Infectious disease HPV Preventive medicine

Additional relevant MeSH terms:

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Uterine Cervical Neoplasms Uterine Neoplasms Genital Neoplasms, Female Urogenital Neoplasms Neoplasms by Site Neoplasms Uterine Cervical Diseases Uterine Diseases Curcumin Anti-Inflammatory Agents, Non-Steroidal	Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Physiological Effects of Drugs Anti-Inflammatory Agents Antirheumatic Agents Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action

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