Curcumin for Precancerous Anal Cells

Recruiting at 1 trial location

Overseen By Lisa Flowers, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Lisa Flowers

Disqualifiers: Coronary disease, Congestive heart failure, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether curcumin, a natural compound, can reverse precancerous anal cells in people with HIV. The goal is to find a gentler treatment for these cells, avoiding more invasive options like surgery. Participants will use different doses of curcumin capsules inserted anally for two weeks. Those diagnosed with anal intraepithelial neoplasia (AIN) 2 or 3 who have not yet received treatment might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative approach.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that curcumin is generally safe for people. Studies have tested doses as high as 12 grams per day for up to three months without major safety issues. Curcumin is usually well-tolerated, with only mild side effects such as stomach upset or diarrhea reported in some cases. This suggests it is likely safe for shorter periods and lower doses, like those tested in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for precancerous anal conditions, which often involve topical chemotherapies or surgical interventions, curcumin offers a novel approach by using a natural compound commonly found in turmeric. Researchers are excited about curcumin because it has anti-inflammatory and antioxidant properties, which may help prevent the progression of precancerous cells. Additionally, this treatment is unique because it is administered intra-anally through gelatin capsules, potentially providing direct localized action with reduced systemic side effects. This innovative delivery method could offer a more targeted and less invasive option compared to traditional approaches.

What evidence suggests that curcumin might be an effective treatment for anal precancerous cells?

Research has shown that curcumin might help treat early signs of cancer. Studies have found that curcumin can reduce the number and size of polyps, small growths that can turn into cancer, within three months. Curcumin has also shown potential benefits against various cancers, such as colorectal, pancreatic, and breast cancer. This suggests it might help protect cells from becoming cancerous. In this trial, participants will receive different doses of curcumin to evaluate its potential to manage or reverse high-grade anal precancerous cells (aHSIL) and possibly prevent them from turning into cancer. ^{2 3 5 6 7}

Who Is on the Research Team?

Lisa Flowers, MD, MPH

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for individuals with HIV who have high-grade squamous intraepithelial lesions (aHSIL) in the anal area, which are precancerous cells. The study aims to help those seeking alternatives to current treatments like ablation or surgery that come with side effects.

Inclusion Criteria

Other inclusion criteria apply

Able and willing to complete Study Diary

My biopsy showed I have AIN 2 or AIN 3.

Exclusion Criteria

Have Grade 2 or higher renal or hematology abnormality

Other exclusion criteria apply

Pregnant or planning to become pregnant in the next three months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive increasing doses of curcumin intra-anally for 14 days following a 3 + 3 dose escalation model

2 weeks

Daily administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, including toxicity and anoscopy changes

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Curcumin

Trial Overview The trial is testing whether curcumin, a natural compound often found in turmeric, can reverse aHSIL and prevent progression to cancer. Participants will receive curcumin treatment and be monitored for its effectiveness against these pre-cancerous cells.

How Is the Trial Designed?

Group I: Dose Level 8 Experimental Treatment 1 Intervention

Participants will receive a supply of curcumin gelatin capsules to insert 4000 mg intra-anally every day for a 14-day treatment period

Group II: Dose Level 7 Experimental Treatment 1 Intervention

Participants will receive a supply of curcumin gelatin capsules to insert 3500 mg intra-anally every day for a 14-day treatment period

Group III: Dose Level 6 Experimental Treatment 1 Intervention

Participants will receive a supply of curcumin gelatin capsules to insert 3000 mg intra-anally every day for a 14-day treatment period

Group IV: Dose Level 5 Experimental Treatment 1 Intervention

Participants will receive a supply of curcumin gelatin capsules to insert 2500 mg intra-anally every day for a 14-day treatment period

Group V: Dose Level 4 Experimental Treatment 1 Intervention

Participants will receive a supply of curcumin gelatin capsules to insert 2000 mg intra-anally every day for a 14-day treatment period

Group VI: Dose Level 3 Experimental Treatment 1 Intervention

Participants will receive a supply of curcumin gelatin capsules to insert 1500 mg intra-anally every day for a 14-day treatment period

Group VII: Dose Level 2 Experimental Treatment 1 Intervention

Participants will receive a supply of curcumin gelatin capsules to insert 1000 mg intra-anally every day for a 14-day treatment period

Group VIII: Dose Level 1 Experimental Treatment 1 Intervention

Participants will receive a supply of curcumin gelatin capsules to insert 500 mg intra-anally every day for a 14-day treatment period

Curcumin is already approved in United States, European Union, India, China for the following indications:

Approved in United States as Curcumin for:

• Dietary Supplement

Approved in European Union as Curcuma for:

• Herbal Medicinal Product

Approved in India as Haldi for:

• Traditional Medicine

Approved in China as Jiang Huang for:

• Traditional Chinese Medicine

Who Is Running the Clinical Trial?

Lisa Flowers

Lead Sponsor

Trials

4

Recruited

760+

Published Research Related to This Trial

Curcumin, derived from turmeric, shows promise as an anticancer and anti-inflammatory agent based on various in-vitro and in-vivo studies, as well as clinical trials conducted from 2011 to 2015.

While curcumin formulations like nanoparticles and liposomes are being developed to improve its effectiveness, clinical trials have demonstrated its safety and tolerability, though the overall efficacy remains uncertain due to small sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An update on Curcuma as a functional food in the control of cancer and inflammation. Schaffer, M., Schaffer, PM., Bar-Sela, G.[2016]

The addition of 2 g of oral curcumin to FOLFOX chemotherapy was found to be safe and well-tolerated in a phase IIa trial involving 28 patients with metastatic colorectal cancer, with similar adverse event profiles between the two treatment groups.

Patients receiving curcumin alongside FOLFOX showed improved overall survival (502 days) compared to those on FOLFOX alone (200 days), although progression-free survival did not reach statistical significance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin Combined with FOLFOX Chemotherapy Is Safe and Tolerable in Patients with Metastatic Colorectal Cancer in a Randomized Phase IIa Trial. Howells, LM., Iwuji, COO., Irving, GRB., et al.[2023]

Curcumin effectively inhibits the growth and spread of breast cancer stem-like cells (BCSCs) by reducing their ability to proliferate, migrate, and invade, as demonstrated in both MCF-7 and MDA-MB-231 cell lines.

The compound also alters the expression of key genes involved in epithelial-mesenchymal transition (EMT) and stem cell characteristics, suggesting that curcumin may serve as a promising anti-metastasis agent for breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-metastasis activity of curcumin against breast cancer via the inhibition of stem cell-like properties and EMT. Hu, C., Li, M., Guo, T., et al.[2019]

Curcumin and its structural analogues (GO-Y030, FLLL-11, and FLLL-12) were tested on three human colorectal cancer cell lines, showing that the analogues were significantly more effective than curcumin in inhibiting cell viability, with IC50 values as low as 0.51 microM compared to curcumin's 10.26-13.31 microM.

The analogues also induced apoptosis more effectively than curcumin, indicated by increased levels of cleaved PARP and caspase-3, while demonstrating low toxicity to normal human lung fibroblasts, suggesting their potential as safer therapeutic options for colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New structural analogues of curcumin exhibit potent growth suppressive activity in human colorectal carcinoma cells. Cen, L., Hutzen, B., Ball, S., et al.[2022]

Curcumin, a natural compound from turmeric, has shown multiple beneficial properties including anti-inflammatory and anti-cancer effects, and it is considered safe even in high doses.

Recent studies suggest that curcumin can enhance the effectiveness of radiation therapy while also protecting normal tissues from radiation damage, making it a promising adjunct treatment in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumins antineoplastic, radiosensitizing and radioprotective properties. Cihan, YB.[2022]

Curcumin and crocin, when used together, significantly reduce the viability of colorectal cancer cells (SW-480) and induce apoptosis by affecting key genes involved in cell death and proliferation.

The combination of these compounds not only promotes cell cycle arrest and autophagy but also decreases the ability of cancer cells to form new colonies, suggesting a promising therapeutic strategy against colorectal cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic anticancer effects of curcumin and crocin on human colorectal cancer cells. Hosseini, SS., Reihani, RZ., Doustvandi, MA., et al.[2022]

The study identified 10 key components in turmeric extract, with major constituents including α-zingiberene and curcumin, which contribute to its potential health benefits.

Turmeric extract demonstrated significant anticancer activity, showing over 95% inhibition of cancer cell growth at a concentration of 250 µg/mL, particularly against HeLa and LX2 cell lines, indicating its promise as a natural cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine. Abualhasan, M., Jaradat, N., Hawash, M., et al.[2023]

Quercetin-decorated liposomes containing curcumin showed improved effectiveness in increasing the lifespan and body weight of mice with Dalton's ascites lymphoma compared to liposomes without quercetin, indicating enhanced therapeutic potential.

The study demonstrated that these liposomes, with a particle size of approximately 261.8 nm, not only improved the cytotoxicity against cancer cells (HT-29 and HCT-15) but also addressed curcumin's limitations like poor solubility and short biological half-life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quercetin-Decorated Curcumin Liposome Design for Cancer Therapy: In-Vitro and In-Vivo Studies. Ravichandiran, V., Masilamani, K., Senthilnathan, B., et al.[2018]

Curcumin, the active compound in turmeric, has been shown to have multiple health benefits, including anti-inflammatory and anticancer properties, by regulating various proteins and enzymes involved in cell growth and survival.

Clinical trials indicate that curcumin is safe for consumption at high doses (up to 12g daily for 3 months) and may have therapeutic potential in treating a variety of diseases, including cancer, inflammatory bowel disease, and arthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin as "Curecumin": from kitchen to clinic. Goel, A., Kunnumakkara, AB., Aggarwal, BB.[2022]

Curcuma longa, commonly known as turmeric, is a medicinal herb with a long history of use in traditional Chinese and Ayurvedic medicine for its anti-inflammatory properties and treatment of various ailments.

Current research highlights turmeric's potential health benefits, including its antioxidant, hepatoprotective, and antimicrobial effects, making it relevant for conditions like cardiovascular disease and gastrointestinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcuma longa (turmeric). Monograph. [2022]

Curcuma species, particularly C. longa, C. aromatica, and C. xanthorrhiza, are widely used in traditional medicine for treating various health issues, including indigestion and diabetes, due to their active compounds like curcumin.

Research from 1976 to 2008 highlights curcumin's significant anti-inflammatory, antioxidant, and potential anti-cancer properties, revealing its therapeutic mechanisms and genomic effects, which support its use in modern medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in the investigation of curcuminoids. Itokawa, H., Shi, Q., Akiyama, T., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06626230

Study Details | NCT06626230 | Safety of Anal Curcumin The purpose of this study is to see if curcumin can reverse anal high-grade squamous intraepithelial lesions (aHSIL) (high-grade anal precancerous cells or ...

2. cancer.gov cancer.gov/about-cancer/treatment/cam/hp/curcumin-pdq

Curcumin and Cancer (PDQ®) - NCI At 3 months, four of five patients had a decrease in polyp number and size from baseline.

3. ctv.veeva.com ctv.veeva.com/study/safety-of-anal-curcumin

Safety of Anal Curcumin - ClinicalTrials.Veeva The purpose of this study is to see if curcumin can reverse anal high-grade squamous intraepithelial lesions (aHSIL) (high-grade anal ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3535097/

Therapeutic Roles of Curcumin: Lessons Learned from ... Since then, curcumin, either alone or in combination with other agents, has demonstrated potential against colorectal cancer, pancreatic cancer, breast cancer, ...

5. withpower.com withpower.com/trial/curcumin-for-precancerous-anal-cells-18cf4

Curcumin for Precancerous Anal Cells Trial Overview The trial is testing whether curcumin, a natural compound often found in turmeric, can reverse aHSIL and prevent progression to cancer.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06626230

Study Details | NCT06626230 | Safety of Anal Curcumin The purpose of this study is to see if curcumin can reverse anal high-grade squamous intraepithelial lesions (aHSIL) (high-grade anal precancerous cells or ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9072734/

Anticancer Properties of Curcumin Against Colorectal Cancer Curcumin has been demonstrated to suppress colon cancer cell development by lowering EGFR expression, which is mediated by a decrease in Egr-1 ...