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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
Sponsor:
Information provided by (Responsible Party):
Lisa Flowers, Emory University

Tracking Information
First Submitted Date  ICMJE December 26, 2019
First Posted Date  ICMJE February 12, 2020
Last Update Posted Date July 13, 2021
Estimated Study Start Date  ICMJE December 2021
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 11, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 11, 2020)
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: February 11, 2020)
Participant Discontinuation [ Time Frame: Month 6 ]
The treatment will be considered tolerable if 25% or fewer of participants discontinue the study early.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Topical Curcumin for HPV Related Cervical Disease
Official Title  ICMJE An Investigation in the Use of Curcumin Topical Herbal Agent for the Treatment of Cervical Intraepithelial Neoplasia
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Neoplasm Cervix
Intervention  ICMJE
  • 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.

  • 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.

Study Arms  ICMJE
  • Experimental: Curcumin Arm
    Participants in this arm will use 2000 mg of intravaginal curcumin once a week for 20 weeks
    Intervention: Drug: Curcumin C3 Complex
  • Placebo Comparator: Placebo Arm
    Participants in this arm will use 2000 mg of intravaginal placebo once a week for 20 weeks
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: February 11, 2020)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Rachael Abraham, PhD 404-251-8940 rfaraha@emory.edu
Contact: Fletcher Neale 305-797-6397 michael.fletcher.neale.jr@emory.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04266275
Other Study ID Numbers  ICMJE STUDY00000758
IRB00117251 ( Other Identifier: Emory Previous IRB number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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.
Responsible Party Lisa Flowers, Emory University
Study Sponsor  ICMJE Lisa Flowers
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Lisa Flowers, MD Emory University
PRS Account Emory University
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP