Trial Outcomes & Findings for Topical Curcumin for Precancer Cervical Lesions (NCT NCT02944578)

NCT ID: NCT02944578

Last Updated: 2024-10-29

Results Overview

Vaginal samples were 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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

Baseline, Weeks 4, 8, 12, and 16

Results posted on

2024-10-29

Participant Flow

Participants were recruited from Grady Hospital Ponce De Leon Center in Atlanta Georgia, USA. Participant enrollment began November 20, 2017 and all follow-up assessments were completed by October 30, 2018. The study was suspended for several years due to participant feedback about using the suppository tablets and then the coronavirus disease 2019 (COVID-19) pandemic, and the study was ultimately terminated in April 2024.

Participant milestones

Participant milestones
Measure
Curcumin
Participants using 2000 mg of intravaginal curcumin capsules once a week for 12 weeks.
Placebo
Participants using 2000 mg of intravaginal placebo capsules once a week for 12 weeks.
Overall Study
STARTED
4
3
Overall Study
COMPLETED
3
3
Overall Study
NOT COMPLETED
1
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Curcumin
Participants using 2000 mg of intravaginal curcumin capsules once a week for 12 weeks.
Placebo
Participants using 2000 mg of intravaginal placebo capsules once a week for 12 weeks.
Overall Study
Physician Decision
1
0

Baseline Characteristics

Topical Curcumin for Precancer Cervical Lesions

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Curcumin
n=4 Participants
Participants using 2000 mg of intravaginal curcumin capsules once a week for 12 weeks.
Placebo
n=3 Participants
Participants using 2000 mg of intravaginal placebo capsules once a week for 12 weeks.
Total
n=7 Participants
Total of all reporting groups
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
4 Participants
n=5 Participants
2 Participants
n=7 Participants
6 Participants
n=5 Participants
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
4 Participants
n=5 Participants
3 Participants
n=7 Participants
7 Participants
n=5 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Sex: Female, Male
Female
4 Participants
n=5 Participants
3 Participants
n=7 Participants
7 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
0 Participants
n=7 Participants
1 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
3 Participants
n=5 Participants
3 Participants
n=7 Participants
6 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
White
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
Region of Enrollment
United States
4 Participants
n=5 Participants
3 Participants
n=7 Participants
7 Participants
n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Weeks 4, 8, 12, and 16

Population: This analysis includes participants who attended the indicated study visit; some participants missed some visits.

Vaginal samples were 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.

Outcome measures

Outcome measures
Measure
Curcumin
n=4 Participants
Participants using 2000 mg of intravaginal curcumin capsules once a week for 12 weeks.
Placebo
n=3 Participants
Participants using 2000 mg of intravaginal placebo capsules once a week for 12 weeks.
Number of Participants With Human Papillomavirus (HPV) Related Molecular Target HPV E6/E7 Messenger Ribonucleic Acid (mRNA) Expression Within HSIL Lesions of the Cervix
Baseline
0 Participants
1 Participants
Number of Participants With Human Papillomavirus (HPV) Related Molecular Target HPV E6/E7 Messenger Ribonucleic Acid (mRNA) Expression Within HSIL Lesions of the Cervix
Week 4
0 Participants
0 Participants
Number of Participants With Human Papillomavirus (HPV) Related Molecular Target HPV E6/E7 Messenger Ribonucleic Acid (mRNA) Expression Within HSIL Lesions of the Cervix
Week 8
0 Participants
0 Participants
Number of Participants With Human Papillomavirus (HPV) Related Molecular Target HPV E6/E7 Messenger Ribonucleic Acid (mRNA) Expression Within HSIL Lesions of the Cervix
Week 12
0 Participants
0 Participants
Number of Participants With Human Papillomavirus (HPV) Related Molecular Target HPV E6/E7 Messenger Ribonucleic Acid (mRNA) Expression Within HSIL Lesions of the Cervix
Week 16
0 Participants
0 Participants

SECONDARY outcome

Timeframe: Weeks 4, 8, 12, and 16

Population: Study enrollment stopped early and the focus of the study shifted to analysis of the primary outcome measure among current participants. Samples for analysis of curcumin in cervical tissue were not collected from any participants.

Vaginal sampling and colposcopy with targeted cervical biopsies will be examined to establish the level of curcumin penetration in cervical tissue, as well as the cumulative effect of daily curcumin over time.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 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.

Outcome measures

Outcome data not reported

Adverse Events

Curcumin

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Lisa Flowers

Emory University

Phone: 404-251-8931

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place