- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02944578
Topical Curcumin for Precancer Cervical Lesions
Biomolecular Effects of Topical Curcumin in HSIL Cervical Neoplasia
Study Overview
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 in HIV-infected women due to immunosuppression and cervical cancer is 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 cervical cancer after HPV exposure entail treatment at the most severe premalignant state (high grade squamous intraepithelial lesion or HSIL). As this procedure is expensive and not widely available in resource-limited areas there is a need for an inexpensive, non-invasive alternative method to treat these premalignant cervical lesions.
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.
This study will explore the effect of curcumin as a potential medical treatment in HIV-infected women with HSIL lesions of the cervix. 40 women with high grade squamous intraepithelial lesion (HSIL) of the cervix will be enrolled to either insert 2000 mg capsule of curcumin or a placebo in their vagina once a week for 12 weeks. After a 4 week long washout period the participants will then undergo removal of the precancerous cells as recommended standard of care. Participants will have regular monthly visits for the duration of the study.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Georgia
-
Atlanta, Georgia, United States, 30303
- Grady Memorial Hospital
-
Atlanta, Georgia, United States, 30308
- Grady Hospital - Ponce De Leon Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- HIV positive women and HIV negative women
- HSIL cytology with no invasive features identified on colposcopy or the baseline biopsy
- Compliant on combined antiretrovirals (cART)
- On continuous antiretrovirals with cluster of differentiation 4 (CD4) count >200 cells/ml with sustained undetectable viral load for at least 3 months
- Patient on reliable birth control. Adequate birth control includes: Combined oral contraceptive pill (OCP), Long Lasting Reversible Contraceptive (LARCP), BiLateral Tubal Ligation (BLT) and DepoProvera Shot/Birth control shot.
- Patient willing to conform to the study requirements
- No risk factors for microinvasive disease (no colposcopic features of microinvasion, adequate colposcopy and negative endocervical curettage)
Exclusion Criteria:
- Lactating and pregnant women
- Patient with irregular cycles (more than once a month).
- Previous hysterectomy and/or prior treatment for cervical precancer condition
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Curcumin Arm
Participants in this arm will use 2000 mg of intravaginal curcumin once a week for 12 weeks.
|
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 chemopreventive 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). 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, colposcopies and biopsies will be performed at the Baseline, Week 4, 8, 12 and 16 visits to collect samples to analyze for the study outcomes.
Other Names:
|
Placebo Comparator: Placebo Arm
Participants in this arm will use 2000 mg of a placebo once a week for 12 weeks.
|
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). 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, colposcopies and biopsies will be performed at the Baseline, Week 4, 8, 12 and 16 visits to collect samples to analyze for the study outcomes. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in human papillomavirus (HPV) related molecular target HPV E6/E7 messenger ribonucleic acid (mRNA) expression within HSIL lesions of the cervix
Time Frame: Baseline, Weeks 4, 8, 12, and 16
|
Vaginal sampling and colposcopy with targeted cervical biopsies will be performed at each study visit.
These samples will be used to determine the association between intravaginal curcumin on known HPV-related molecular target HPV E6/E7 mRNA expression within high grade squamous intraepithelial (HSIL) lesions of the cervix in HIV- infected women.
The APTIMA® HPV Assay that will be utilized detects full-length HPV E6/E7 mRNA for HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 and correlates very well with integrated HPV, which in turn correlates with full-length HPV E6/E7 protein levels.
|
Baseline, Weeks 4, 8, 12, and 16
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Quantify curcumin levels in cervical tissue
Time Frame: Baseline, Weeks 4, 8, 12, and 16
|
Vaginal sampling and colposcopy with targeted cervical biopsies will be performed at each study visit.
These samples will be examined to establish the level of curcumin penetration in cervical tissue, as well as the cumulative effect of daily curcumin over time.
|
Baseline, Weeks 4, 8, 12, and 16
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Explore the association between curcumin and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)
Time Frame: Baseline, Weeks 4, 8, 12, and 16
|
Vaginal samples and cervical biopsies, obtained at each study visit, will be used to determine the association between curcumin and known biomarkers of cervical disease.
This exploratory aim seeks to use repeated-measures analyses, utilizing a linear mixed model for the curcumin group to assess the association between nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and the concentration of curcumin at each time point.
NF-κB upregulation is related to the grade of cervical intraepithelial neoplasia (CIN) although the significance of NF-κB activation per se to CIN lesion development and its prognostic value in cervical cancer have not been well defined.
The analysis of NF-κB binding activity will provide a direct molecular benchmark for assessing curcumin treatment responses independent from its therapeutic effects.
|
Baseline, Weeks 4, 8, 12, and 16
|
Explore the association between curcumin and p16INK4a
Time Frame: Baseline, Weeks 4, 8, 12, and 16
|
Vaginal samples and cervical biopsies, obtained at each study visit, will be used to determine the association between curcumin and known biomarkers of cervical disease.
This exploratory aim seeks to use repeated-measures analyses, utilizing a linear mixed model for the curcumin group to assess the association between p16INK4a and the concentration of curcumin at each time point.
p16INK4a (a tumor suppressor protein) is an indirect marker of cell cycle dysregulation and has been shown to be expressed in cervical dysplasias and carcinomas associated with high risk HPV infections.
|
Baseline, Weeks 4, 8, 12, and 16
|
Explore the association between curcumin and Rb
Time Frame: Baseline, Weeks 4, 8, 12, and 16
|
Vaginal samples and cervical biopsies, obtained at each study visit, will be used to determine the association between curcumin and known biomarkers of cervical disease.
This exploratory aim seeks to use repeated-measures analyses, utilizing a linear mixed model for the curcumin group to assess the association between Rb and the concentration of curcumin at each time point.
Rb is an important cell cycle regulator protein in cervical carcinogenesis which is suppressed in most cervical cancer cells.
Increased levels of this protein has been linked to regression of cervical cancer lesions.
|
Baseline, Weeks 4, 8, 12, and 16
|
Explore the association between curcumin and p53
Time Frame: Baseline, Weeks 4, 8, 12, and 16
|
Vaginal samples and cervical biopsies, obtained at each study visit, will be used to determine the association between curcumin and known biomarkers of cervical disease.
This exploratory aim seeks to use repeated-measures analyses, utilizing a linear mixed model for the curcumin group to assess the association between p53 and the concentration of curcumin at each time point.
p53 is an important cell cycle regulator protein in cervical carcinogenesis which is suppressed in most cervical cancer cells.
Increased levels of this protein have been linked to regression of cervical cancer lesions.
|
Baseline, Weeks 4, 8, 12, and 16
|
Explore the association between curcumin and vascular endothelial growth factor (VEGF)
Time Frame: Baseline, Weeks 4, 8, 12, and 16
|
Vaginal samples and cervical biopsies, obtained at each study visit, will be used to determine the association between curcumin and known biomarkers of cervical disease.
This exploratory aim seeks to use repeated-measures analyses, utilizing a linear mixed model for the curcumin group to assess the association between vascular endothelial growth factor (VEGF) and the concentration of curcumin at each time point.
VEGF expression has been shown to correlate with severity of cervical intraepithelial neoplasia (CIN) lesions and invasive disease.
|
Baseline, Weeks 4, 8, 12, and 16
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lisa Flowers, MD, Emory University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antineoplastic Agents
- Curcumin
Other Study ID Numbers
- IRB00079183
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Neoplasms
-
GlaxoSmithKlineCompleted
-
Amphia HospitalRecruitingColonic Neoplasms MalignantNetherlands
-
Marquette General Health SystemUpper Michigan Brain Tumor CenterWithdrawnGlioma | MeningiomaUnited States
-
European Association for Endoscopic SurgeryWithdrawn
-
Ann & Robert H Lurie Children's Hospital of ChicagoCompletedBrain Stem Neoplasms, Primary | Neoplasms, Brain StemUnited States
-
Moscow Clinical Scientific CenterRecruitingCecal Neoplasms | Colonic Neoplasms MalignantRussian Federation
-
GlaxoSmithKlineRecruitingNeoplasms, RectalUnited States, France, Italy, Japan, Spain, United Kingdom, Germany, Korea, Republic of, Canada, Netherlands
-
Russian Society of Colorectal SurgeonsRecruitingNeoplasms,ColorectalRussian Federation
-
Third Affiliated Hospital, Sun Yat-Sen UniversityRecruiting
-
Novartis PharmaceuticalsBayerCompletedColorectal Neoplasms | Rectal Neoplasms | Colonic NeoplasmsUnited States, Germany, Belgium, Canada, Spain, United Kingdom, Taiwan, France, Switzerland, Sweden, Portugal, New Zealand, Italy, Slovakia, Australia, Austria, Brazil, Hong Kong
Clinical Trials on Curcumin
-
H.K.E.S's S.Nijalingappa Institute of Dental Science...Unknown
-
Université de SherbrookeUnknown
-
Daniel DobererCompleted
-
Federico II UniversityCompleted
-
Kaiser PermanenteCompletedIrritable Bowel SyndromeUnited States
-
Woodbury, Michel, M.D.Lawson Health Research InstituteCompletedDepression | Schizophrenia | Schizoaffective DisorderPuerto Rico
-
Gary MorrowNational Cancer Institute (NCI)CompletedPain | Breast Carcinoma | Stage 0 Breast Cancer | Radiation-Induced DermatitisUnited States
-
Emory UniversityCompletedUterine Cervical DysplasiaUnited States
-
Louisiana State University Health Sciences Center...TerminatedMild Cognitive ImpairmentUnited States
-
University of North Carolina, Chapel HillColgate PalmoliveCompletedHalitosisUnited States