Grape Seed Extract for Early Stage Lung Cancer

Recruiting at 1 trial location

Overseen By Jenny T Mao, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: VA Office of Research and Development

Must not be taking: CYP3A4 modulators, Investigational agents

Disqualifiers: Cognitive impairment, Respiratory disease, Angina, 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: 4

Duration: 2-3 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Lung cancer is the leading cause of cancer death in the country, surpassing deaths caused by colorectal, prostate and breast cancers combined. Veterans are at higher risk of lung cancer due to the higher rate of smoking and environmental toxin exposures. The lack of effective therapy for lung cancer provides the impetus to search for alternative, safe, and effective treatment agents to improve treatment strategy against lung cancer, enhance the probability of a cure and reduce recurrence. Based on encouraging preclinical and clinical findings from an early phase I lung cancer prevention study, using a special formulation of a standardized grape seed extract with enhanced absorption called leucoselect phytosome (LP), the purpose of this new CSR\&D Merit Review project is to evaluate the potential usefulness of LP for pre-surgical treatment of early stage lung cancer patients in a phase IIa clinical trial. Findings from this study may set the stage for larger, confirmatory trials in the near future.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that affect cytochrome P450 3A4 unless an alternative can be provided. If you are on such medications, you may need to switch to a different one.

What data supports the effectiveness of the treatment Leucoselect Phytosome for early-stage lung cancer?

Research shows that Leucoselect Phytosome, a grape seed extract combined with soy phospholipids, can reduce cell growth markers in the lungs and increase beneficial fatty acids and anti-inflammatory compounds in the blood, which are linked to cancer prevention. ^{1 2 3 4 5}

Is grape seed extract safe for humans?

Grape seed extract, including forms like Leucoselect Phytosome, has been studied in humans and generally found to be well tolerated, with no major safety concerns reported in clinical trials involving heavy smokers. ^{1 2 3 4 5}

What makes the treatment Leucoselect Phytosome unique for early stage lung cancer?

Leucoselect Phytosome is unique because it combines grape seed extract with soy phospholipids to enhance absorption, and it has shown potential in reducing cell proliferation in the lungs and increasing beneficial omega-3 fatty acids and anti-inflammatory compounds in the blood, which may help prevent lung cancer in smokers. ^{1 2 6 7 8}

Research Team

Jenny T Mao, MD

Principal Investigator

VA San Diego Healthcare System, San Diego, CA

Eligibility Criteria

This trial is for early stage lung cancer patients who can consent, have a good performance status (0-1), normal blood counts and liver function, and lesions likely to be lung cancer. They must not have advanced respiratory disease, be pregnant or breastfeeding, take certain drugs affecting the liver enzyme P450 3A4, or consume more than one glass of wine daily.

Inclusion Criteria

I have suspicious lung lesions.

I am fully active or can carry out light work.

Your complete blood count (CBC) is normal.

Exclusion Criteria

You are currently breastfeeding.

I am taking medication that affects liver enzyme levels and cannot switch.

My lung function is strong enough for surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive 2-3 weeks of oral LP treatment before surgical resection

2-3 weeks

Weekly phone follow-up

Surgery

Surgical resection of tumors with collection of post-treatment samples

Follow-up

Post-surgery follow-up to monitor safety and effectiveness

4 years

Phone follow-up at 3-4 weeks, 6 months, and annually

Treatment Details

Interventions

• Leucoselect Phytosome

Trial Overview The study tests leucoselect phytosome (LP), a grape seed extract with enhanced absorption as pre-surgical treatment for early stage lung cancer. It's based on promising earlier results suggesting LP might improve outcomes and reduce recurrence in these patients.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

All qualified participants meeting entry criteria that are enrolled will receive 2-3 weeks of oral LP treatment.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

Grape seed extract (GSE) effectively inhibits the growth of prostate cancer PC-3 cells in a concentration- and time-dependent manner, suggesting its potential as a treatment for prostate cancer.

In contrast, GSE showed only a mild inhibitory effect on normal kidney cells, indicating a degree of safety for normal tissues while targeting cancer cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Grape seed extract inhibits the growth of prostate cancer PC-3 cells]. Huang, TT., Shang, XJ., Yao, GH., et al.[2008]

A clinical study involving heavy active and former smokers showed that leucoselect phytosome, a grape seed procyanidin extract, significantly reduced bronchial cell proliferation, indicating its potential as a chemopreventive agent against lung cancer.

Treatment with leucoselect phytosome also improved serum levels of beneficial omega-3 fatty acids and their metabolites, which correlated with reduced cell proliferation in lung cancer cell lines, suggesting both cardiovascular and anti-cancer benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leucoselect Phytosome Modulates Serum Eicosapentaenoic Acid, Docosahexaenoic Acid, and Prostaglandin E3 in a Phase I Lung Cancer Chemoprevention Study. Mao, JT., Xue, B., Fan, S., et al.[2022]

A clinical study involving 8 participants (ages 46-68) found that leucoselect phytosome (LP), a grape seed procyanidin extract, was well tolerated over 3 months, with no dose adjustments needed, indicating its safety for use in heavy smokers.

Treatment with LP resulted in a significant 55% reduction in bronchial Ki-67 labeling index, a marker of cell proliferation, suggesting its potential effectiveness as a chemopreventive agent against lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pilot Study of a Grape Seed Procyanidin Extract for Lung Cancer Chemoprevention. Mao, JT., Lu, QY., Xue, B., et al.[2023]

Grape seed procyanidin extract (GSE) has shown potential as an anti-cancer agent by inhibiting pathways related to inflammation and cell proliferation in lung cancer cells, specifically through the modulation of prostacyclin (PGI2) and 15-hydroxyeicosatetraenoic acid (15-HETE).

In a lung cancer chemoprevention trial, GSE not only increased the production of PGI2 and 15-HETE but also demonstrated significant antiproliferative effects on lung premalignant and malignant cells, suggesting its efficacy as a chemopreventive agent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways. Mao, JT., Smoake, J., Park, HK., et al.[2021]

Liofenol™, a natural extract from red wine, significantly reduced the proliferation of colon cancer cells (HCT116) by activating key cell cycle regulators (p53 and p21) and increasing specific sphingolipid mediators, suggesting a potential mechanism for its anti-cancer effects.

The extract also enhanced the antioxidant response through the activation of the Nrf2 transcription factor, promoting differentiation of cancer cells without affecting their sensitivity to chemotherapy, indicating its potential as a supportive dietary intervention in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural grape extracts regulate colon cancer cells malignancy. Signorelli, P., Fabiani, C., Brizzolari, A., et al.[2015]

The combination of grape seed procyanidin extract (GSE) and milk thistle silymarin extract (MTE) significantly inhibited the growth of lung cancer cells in both cell lines and mouse models, demonstrating their potential as an effective treatment against lung cancer.

The study found that GSE and MTE were well-tolerated in mice without causing toxicity, and they worked together to enhance the expression of tumor suppressors miR-663a and FHIT, which are important for their anti-cancer effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer - The role of MiR-663a and FHIT. Mao, JT., Xue, B., Lu, QY., et al.[2023]

Grape seed extract (GSE) induces significant morphological changes in prostate cancer PC-3 cells, including cell shrinkage and membrane damage, indicating its potential effectiveness in cancer treatment.

The study demonstrated that GSE can lead to necrosis and apoptosis in PC-3 cells after 24, 48, and 72 hours of treatment, suggesting it may be a promising natural therapeutic agent against prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Grape seed extract induces morphological changes of prostate cancer PC-3 cells]. Shang, XJ., Yin, HL., Ge, JP., et al.[2009]

High concentrations of grape seed extract (GSE) (50-400 μg/ml) significantly inhibited the growth of oral cancer cells (Ca9-22) and induced apoptosis, while low concentrations (1-10 μg/ml) had only a mild effect.

The study found that higher GSE concentrations increased reactive oxygen species (ROS) production and mitochondrial dysfunction, leading to greater DNA damage in cancer cells, suggesting that GSE's antiproliferative effects are concentration-dependent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage. Yen, CY., Hou, MF., Yang, ZW., et al.[2018]

References

1. China pubmed.ncbi.nlm.nih.gov

[Grape seed extract inhibits the growth of prostate cancer PC-3 cells]. [2008]

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

Leucoselect Phytosome Modulates Serum Eicosapentaenoic Acid, Docosahexaenoic Acid, and Prostaglandin E3 in a Phase I Lung Cancer Chemoprevention Study. [2022]

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

A Pilot Study of a Grape Seed Procyanidin Extract for Lung Cancer Chemoprevention. [2023]

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

Grape Seed Procyanidin Extract Mediates Antineoplastic Effects against Lung Cancer via Modulations of Prostacyclin and 15-HETE Eicosanoid Pathways. [2021]

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

Natural grape extracts regulate colon cancer cells malignancy. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Combinations of grape seed procyanidin extract and milk thistle silymarin extract against lung cancer - The role of MiR-663a and FHIT. [2023]

7. China pubmed.ncbi.nlm.nih.gov

[Grape seed extract induces morphological changes of prostate cancer PC-3 cells]. [2009]

8. England pubmed.ncbi.nlm.nih.gov

Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage. [2018]