Supplements for Frailty in Older Cancer Survivors

(ReFOCUS2 Trial)

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Rochester

Disqualifiers: Chemotherapy, Liver disease, Dementia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

118 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment to help older cancer survivors who feel physically frail. Researchers compare a daily vitamin mix, including EGCG (a compound found in green tea) and Vitamin C (Ascorbic Acid), to a placebo (a harmless sugar pill) to determine if it improves strength and energy. The trial seeks participants aged 65 or older who have survived stage I-III cancer and feel physically weak or tired. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow patients on certain endocrine therapies (Anastrozole, Leuprolide acetate, and Bicalutamide) to enroll.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Epigallocatechin-3-Gallate (EGCG), a compound in green tea, is generally safe for most people. However, some studies have reported rare cases of liver issues linked to green tea, possibly due to individual reactions. The European Food Safety Authority (EFSA) considers daily doses of EGCG up to 800 mg safe. In this trial, participants will receive 800 mg, which is within this safe limit.

Ascorbic Acid, better known as Vitamin C, is commonly used and usually well-tolerated. It is considered safe and is often taken as a dietary supplement without major problems.

In this trial, participants will take 800 mg of EGCG and 250 mg of Vitamin C each day. While there are rare risks with EGCG, the doses in this study remain within established safe limits. Participants should consult a doctor before participating, especially if there are concerns about liver health or past reactions to green tea products. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for frailty in older cancer survivors, which often includes exercise programs and nutritional support, these treatments use powerful compounds like Epigallocatechin-3-Gallate (EGCG) and Ascorbic Acid (Vitamin C). EGCG, a natural antioxidant found in green tea, is known for its anti-inflammatory properties and potential to improve muscle function. Meanwhile, Ascorbic Acid is crucial for collagen production, which can support muscle and tissue repair. Researchers are excited because combining these compounds may offer a novel way to enhance physical resilience and quality of life for older cancer survivors.

What evidence suggests that this trial's treatments could be effective for frailty in older cancer survivors?

Research has shown that a compound called EGCG, found in green tea, might help reduce inflammation and other frailty symptoms in older cancer survivors. EGCG possesses anti-inflammatory properties and may aid in managing frailty. Some studies suggest that EGCG might also slow the growth of cancer cells. In this trial, one group of participants will receive EGCG with Vitamin C, known for boosting the immune system and potentially improving overall health. Another group will receive a placebo of microcrystalline cellulose with Vitamin C. Although more research is needed, these early findings offer promise for managing frailty symptoms. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people over 65 who've had stage I-III cancer, finished treatment within the last 10 years (except ongoing endocrine therapy), and show signs of frailty. They must be able to consent or have a proxy do so. Those with planned chemotherapy, certain liver issues, caffeine allergies, recent major psychiatric events, unmanaged liver disease, high green tea consumption or dementia cannot join.

Inclusion Criteria

I am 65 years old or older.

My cancer is at an early to mid-stage (I-III).

I finished my cancer treatment aimed at curing it within the last 10 years.

Exclusion Criteria

My recent liver tests show levels three times higher than normal.

I have been diagnosed with dementia.

I am scheduled for chemotherapy throughout the study period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 12-week intervention with either EGCG or placebo to assess its effect on physical frailty

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ascorbic Acid (Vitamin C)
• Epigallocatechin-3-Gallate (EGCG)
• Microcrystalline cellulose (MCC)

Trial Overview The study tests if a supplement called EGCG can reduce frailty in older cancer survivors compared to a placebo. Participants are randomly assigned to receive either EGCG or an inactive substance (placebo) for 12 weeks and their physical condition will be monitored.

How Is the Trial Designed?

Group I: Epigallocatechin-3-Gallate (EGCG) Experimental Treatment 2 Interventions

800mg Epigallocatechin-3-Gallate (EGCG) pills AND 250mg Ascorbic Acid (Vitamin C) once daily

Group II: Microcrystalline cellulose (MCC) Placebo Group 2 Interventions

800mg microcrystalline cellulose (MCC) pills AND 250mg Ascorbic Acid (Vitamin C) once daily

Ascorbic Acid (Vitamin C) is already approved in United States for the following indications:

Approved in United States as Ascor for:

• Short-term treatment of scurvy in adult and pediatric patients age 5 months and older for whom oral administration is not possible, insufficient or contraindicated

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Published Research Related to This Trial

In a study of 14 elderly patients, those with low leucocyte ascorbic acid levels (below 15 µg/10^8 white blood cells) showed an increase in urinary hydroxyproline/creatinine ratios after receiving 1 g of ascorbic acid daily for six days, indicating improved collagen metabolism.

The results suggest that elderly patients with low ascorbic acid levels may have impaired collagen metabolism and should be considered for ascorbic acid supplementation to support their health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urinary hydroxyproline in the elderly with low leucocyte ascorbic acid levels. Windsor, AC., Williams, CB.[2019]

Ascorbic acid significantly inhibited the growth of human mammary tumors in mice when administered in drinking water, indicating its potential as an antitumor agent.

The combination of ascorbic acid and cupric sulfate was more effective in suppressing tumor growth than either substance alone, suggesting that certain degradation products of ascorbic acid may have active antineoplastic properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibiting effect of ascorbic acid on the growth of human mammary tumor xenografts. Tsao, CS.[2018]

In a study involving C57BL/6 mice with implanted Lewis lung carcinoma, the combination of ascorbic acid with mitomycin C and 5-fluorouracil significantly inhibited tumor growth compared to other treatment groups, showing the potential for enhanced antitumor activity.

Histological analysis revealed degenerative changes in tumor tissues after treatment with the combination therapy, indicating that ascorbic acid may enhance the effectiveness of traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of ascorbic acid in combination with antitumor agents against Lewis lung carcinoma. Nakano, K., Fujimoto, S., Tokita, H.[2013]

Ascorbic acid (AA) and its derivative 6-chloro-6-deoxy ascorbic acid (6-Cl-AA) were found to inhibit the growth of specific cancer cell lines, including HeLa and SK-BR-3 cells, suggesting their potential as antitumor agents.

6-Cl-AA demonstrated a stronger inhibitory effect on certain chemotherapy-resistant cancer cells, such as HeLa cells resistant to cisplatin and SK-BR-3 cells resistant to doxorubicin, indicating its potential for treating resistant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ascorbic acid and 6-deoxy-6-chloro-ascorbic acid: potential anticancer drugs. Osmak, M., Kovacek, I., Ljubenkov, I., et al.[2013]

Magnesium ascorbyl-2-phosphate is as effective as ascorbic acid in stimulating collagen synthesis in dermal fibroblasts, making it a suitable alternative for experiments requiring stable conditions.

The sodium salt of ascorbyl-2-phosphate is less effective, needing a tenfold higher concentration to match the collagen synthesis stimulation of ascorbic acid, highlighting the importance of choosing the right form for research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of collagen synthesis in human dermal fibroblasts by the sodium and magnesium salts of ascorbyl-2-phosphate. Geesin, JC., Gordon, JS., Berg, RA.[2019]

6-O-palmitoyl ascorbate significantly enhances collagen synthesis and increases procollagen mRNA levels in human intestinal smooth muscle cells more effectively than L-ascorbate, with a twofold increase observed at lower concentrations (2.5 and 5 microM).

Both 6-O-palmitoyl ascorbate and L-ascorbate lead to similar increases in collagen secretion at higher concentrations (20 microM), but palmitoyl ascorbate's superior efficacy may be due to its greater resistance to oxidation, making it a promising agent for collagen synthesis studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palmitoyl ascorbate: selective augmentation of procollagen mRNA expression compared with L-ascorbate in human intestinal smooth muscle cells. Rosenblat, G., Willey, A., Zhu, YN., et al.[2013]

Oral or injected ascorbic acid supplements significantly increased plasma ascorbic acid levels in mice, but did not affect the induction or progression of AA amyloidosis, a serious condition with no specific treatment.

The study tested ascorbic acid's effects on amyloidosis induction in mice using two different methods, but ultimately found no beneficial impact on the disease despite higher vitamin C levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The failure of ascorbic acid therapy to alter the induction or remission of murine amyloidosis. Baltz, ML., Caspi, D., Glatthaar, BE., et al.[2018]

In a study of 186 elderly individuals, a significant percentage (around 39% to 47%) were found to have ascorbic acid deficiency, indicating a widespread issue of low vitamin C status among this population.

Those receiving multivitamin supplements had adequate plasma ascorbic acid levels, suggesting that supplementation can effectively prevent vitamin C deficiency, especially since no clinical symptoms were observed despite low biochemical levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C status of institutionalised and non-institutionalised aged. Vir, SC., Love, AH.[2013]

Ascorbic acid (vitamin C) plays a crucial role in enhancing the body's resistance to cancer by stabilizing tissue and supporting immune functions, which may help protect against cancer progression.

Recent clinical trials suggest that supplemental ascorbate could have therapeutic value in cancer treatment, potentially leading to its inclusion in standard cancer care protocols in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin C and cancer: an overview. Cameron, E.[2013]

High-dose intravenous ascorbate (vitamin C) significantly reduces the survival of gastric adenocarcinoma cells by 70-85% in a dose-dependent manner, while showing low toxicity to normal intestinal cells, indicating its potential as a targeted cancer treatment.

When combined with standard chemotherapy and radiation treatments, pharmacological ascorbate enhances the effectiveness of these therapies and improves overall survival in mice with gastric cancer, suggesting it could be a valuable adjuvant in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological Ascorbate as an Adjuvant for Enhancing Radiation-Chemotherapy Responses in Gastric Adenocarcinoma. O'Leary, BR., Houwen, FK., Johnson, CL., et al.[2019]

Vitamin C (ascorbate) can effectively induce cell death in tumor cells, particularly in the SW620 hollow fiber model, with a significant increase in apoptotic cells observed at a concentration of 10 mM after 2 days of treatment.

Combining ascorbate with lipoic acid significantly enhances its anti-cancer effects, reducing the lethal concentration needed to kill tumor cells from 34 mM to 4 mM, suggesting that such combinations could be a promising strategy for cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Casciari, JJ., Riordan, NH., Schmidt, TL., et al.[2018]

Pharmacologic doses of ascorbic acid (1-3 mM) can inhibit the growth of colon cancer cells and induce cell death through mechanisms involving the downregulation of specific transcription factors (Sp1, Sp3, and Sp4).

The anticancer effects of ascorbic acid are linked to its ability to generate reactive oxygen species (ROS), which leads to decreased expression of genes that promote cancer cell proliferation, survival, and angiogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic doses of ascorbic acid repress specificity protein (Sp) transcription factors and Sp-regulated genes in colon cancer cells. Pathi, SS., Lei, P., Sreevalsan, S., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10343677/

Epigallocatechin-3-Gallate Therapeutic Potential in Cancer It has been demonstrated that EGCG may exert anti-proliferative, anti-inflammatory, and apoptosis-inducing effects or induce epigenetic changes.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04553666

Reducing Frailty for Older Cancer Survivors Using ... To determine adherence of a two arm randomized clinical trial of EGCG supplementation in older survivors of cancer by determining the proportion of participants ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-06012

Epigallocatechin Gallate Compared to Placebo for ... Epigallocatechin gallate may reduce inflammation and other frailty symptoms in older cancer survivors. Eligibility Criteria ...

4. researchgate.net researchgate.net/publication/394785782_Green_Tea_and_Epigallocatechin_Gallate_EGCG_for_Cancer_Prevention_A_Systematic_Review_and_Meta-Analysis

Green Tea and Epigallocatechin Gallate (EGCG) for ... Previous studies have reported inconsistent effects of green tea and its extract, epigallocatechin gallate (EGCG), on cancer prevention.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3509513/

Epigallocatechin Gallate (EGCG) Is the Most Effective Cancer ... Our previous study showed that EGCG enhanced the effects of ginseng compounds in the inhibition of colon cancer cell growth, indicating that ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7009618/

Scientific opinion on the safety of green tea catechins - PMC However, rare cases of liver injury have been reported after consumption of green tea infusions, most probably due to an idiosyncratic reaction. Based on the ...

7. cot.food.gov.uk cot.food.gov.uk/%20Third%20Draft%20Statement%20on%20the%20Hepatotoxicity%20of%20Green%20Tea%20Catechins

Third Draft Statement on the Hepatotoxicity of Green Tea ... The COT noted that a daily dose corresponding to 375 mg EGCG is somewhat lower than the 'safe' limit of 800 mg described by EFSA . 50. In 2009, ...

8. scitechdaily.com scitechdaily.com/not-safe-for-everybody-the-hidden-risk-of-green-tea-extract/

Not Safe for Everybody: The Hidden Risk of Green Tea ... New research suggests that green tea extract can cause liver damage in a small subset of the population.