A Study to Evaluate the Safety and Efficacy of RQC for AMD

Overseen By Stephanie Aman, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Paul A Knepper, MD PhD

Must not be taking: Anticoagulants

Disqualifiers: Wet AMD, Alzheimer's, Dementia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 24 months

150 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any anticoagulant medication (blood thinners) at least 5 days before starting the study. For other medications, the protocol does not specify if you need to stop taking them.

What data supports the effectiveness of the drug curcumin?

Research shows that curcumin, a compound found in turmeric, has anti-inflammatory and antioxidant properties, which may help in managing chronic diseases like diabetes and certain cancers. However, its low solubility and bioavailability in the body can limit its effectiveness as a treatment. ^{1 2 3 4 5}

Is the treatment generally safe for human use?

Research indicates that various forms of turmeric and curcumin, including tetrahydrocurcuminoids and CuminUP60®, are generally safe for human use. Studies have shown no concerns regarding genotoxicity (damage to genetic information) and have established safe consumption levels. For example, tetrahydrocurcuminoids are considered safe at 140 mg/day for adults, and CuminUP60® has a no observed adverse effect level (NOAEL) of 1000 mg/kg body weight per day in rats. ^{4 6 7 8 9}

How does the treatment with Curcumin, Quercetin, and Resveratrol differ from other treatments?

This treatment is unique because it combines natural compounds known for their antioxidant and anti-inflammatory properties, which may help in managing various conditions. Curcumin, derived from turmeric, has been extensively studied for its potential to regulate inflammation and oxidative stress, while Quercetin and Resveratrol are known for their roles in protecting cells from damage and supporting cardiovascular health. This combination may offer a novel approach by targeting multiple pathways involved in disease processes. ^{4 5 10 11 12}

What is the purpose of this trial?

This study is evaluating whether a combination of resveratrol, quercetin, and curcumin is safe and effective for people with age-related macular degeneration.

Research Team

Paul A Knepper, MD, PhD

Principal Investigator

Zaparackas Knepper, Ltd

Zibute Zaparackas, MD

Principal Investigator

Zaparackas Knepper, Ltd

Eligibility Criteria

Inclusion Criteria

Male or female of any race or ethnicity.

Aged 50-90 years at time of study entry.

Ability to speak, read, and understand English.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either RQC or curcumin alone for AMD over 24 months

24 months

Follow-up visits at least every 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Curcumin
• Quercetin
• Resveratrol

Participant Groups

Group I: Resveratrol, Quercetin, Curcumin (RQC) Experimental Treatment 1 Intervention

Resveratrol (100mg BID), Quercetin (120mg BID), Curcumin (1000mg BID); 24 months

Group II: Curcumin Active Control 1 Intervention

Curcumin (1000mg BID); 24 months

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?

Paul A Knepper, MD PhD

Lead Sponsor

Trials

1

Recruited

150+

Findings from Research

Curcumin, the active compound in turmeric, has demonstrated a wide range of therapeutic effects, including antioxidant, anti-inflammatory, and anticancer properties, making it potentially beneficial for various chronic diseases such as diabetes, arthritis, and Alzheimer's disease.

Research indicates that curcumin's effects are mediated through the regulation of key biological pathways, similar to those targeted by modern medications like tumor necrosis factor blockers and growth factor inhibitors, suggesting its role as a multitargeted therapeutic agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin: the Indian solid gold. Aggarwal, BB., Sundaram, C., Malani, N., et al.[2022]

Curcumin, the active compound in turmeric, has shown significant therapeutic properties, including anti-inflammatory, antioxidant, and cancer preventive effects, making it a promising treatment for chronic diseases like diabetes mellitus.

Despite its potential benefits, curcumin's low solubility in water limits its bioavailability, which poses challenges for its use as a therapeutic agent; ongoing research aims to improve its solubility and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CURCUMA LONGA AS MEDICINAL HERB IN THE TREATMENT OF DIABET- IC COMPLICATIONS. Karlowicz-Bodalska, K., Han, S., Freier, J., et al.[2018]

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]

Tetrahydrocurcuminoids from turmeric have been evaluated and deemed safe for consumption at a maximum level of 140 mg/day for adults, which is lower than the proposed dose of 300 mg/day.

The evaluation included a 90-day oral toxicity study and showed no concerns regarding genotoxicity, indicating that tetrahydrocurcuminoids do not pose significant health risks when consumed within the established safe limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food pursuant to Regulation (EU) 2015/2283. Turck, D., Bohn, T., Castenmiller, J., et al.[2022]

CuminUP60®, a curcumin complex derived from Curcuma longa L., demonstrated no mutagenic effects in various safety studies, indicating it is safe for use.

In toxicity studies involving Sprague-Dawley rats, a single dose of 5000 mg was well tolerated, and the no observed adverse effect level (NOAEL) was established at 1000 mg/kg bw/day over a 4-week period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of CuminUP60® - A novel curcumin complex. Dziwenka, M., Li, X., Li, W., et al.[2022]

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]

The safety evaluation of CURCUGEN®, an oleoresin-based turmeric extract, showed a very high tolerance in Sprague-Dawley rats, with an LD50 greater than 5000 mg/kg body weight, indicating low toxicity.

In a 90-day study, CURCUGEN® demonstrated a no observed adverse effect level (NOAEL) of 2000 mg/kg body weight/day and did not show any genotoxic or clastogenic effects, confirming its safety for potential use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Oleoresin-Based Turmeric Formulation: Assessment of Genotoxicity and Acute and Subchronic Oral Toxicity. Nirvanashetty, S., Panda, SK., Jackson-Michel, S.[2022]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Curcumin: the Indian solid gold. [2022]

2. Poland pubmed.ncbi.nlm.nih.gov

CURCUMA LONGA AS MEDICINAL HERB IN THE TREATMENT OF DIABET- IC COMPLICATIONS. [2018]

3. England pubmed.ncbi.nlm.nih.gov

High-sensitivity determination of curcumin in human urine using gemini zwitterionic surfactant as a probe by resonance light scattering technique. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Recent advances in the investigation of curcuminoids. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Effect of curcumin on dexamethasone-induced testicular toxicity in mice. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of tetrahydrocurcuminoids from turmeric (Curcuma longa L.) as a novel food pursuant to Regulation (EU) 2015/2283. [2022]

7. Ireland pubmed.ncbi.nlm.nih.gov

Safety evaluation of CuminUP60® - A novel curcumin complex. [2022]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Quercetin-Decorated Curcumin Liposome Design for Cancer Therapy: In-Vitro and In-Vivo Studies. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Safety Evaluation of Oleoresin-Based Turmeric Formulation: Assessment of Genotoxicity and Acute and Subchronic Oral Toxicity. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Curcumin and its analogues as potent inhibitors of low density lipoprotein oxidation: H-atom abstraction from the phenolic groups and possible involvement of the 4-hydroxy-3-methoxyphenyl groups. [2013]

11. United States pubmed.ncbi.nlm.nih.gov

Modulation of Hepatic Cytochrome P450 Enzymes by Curcumin and its Pharmacokinetic Consequences in Sprague-dawley Rats. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Curcumin as "Curecumin": from kitchen to clinic. [2022]