Nutraceuticals for Neurofibromatosis

Overseen By Fullenkamp Fullenkamp

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Selumetinib, MAPK inhibitors

Disqualifiers: Immunosuppression, Swallowing difficulties, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how curcumin (a compound found in turmeric) and high phenolic extra virgin olive oil (HP-EVOO) might benefit people with neurofibromatosis type 1 (NF1), a genetic disorder that causes tumors on nerve tissue. The study examines different dose levels of curcumin to assess their interaction with HP-EVOO when taken together. Participants will take these supplements twice daily on an empty stomach for up to a year. This trial suits adults diagnosed with NF1 who have noticeable skin tumors and have not recently used similar treatments. 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 new treatment.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications like selumetinib or other MAPK, MEK, or mTOR inhibitors, as well as chemotherapy or radiation. If you are on these treatments, you would need to stop them to participate in the trial.

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

Research has shown that curcumin and high phenolic extra virgin olive oil (HP-EVOO) are under study for their safety and effectiveness in treating conditions like neurofibromatosis. Studies have found that these treatments can be used for up to a year without causing serious side effects.

Curcumin, a substance in turmeric, is known for reducing inflammation. HP-EVOO, a type of olive oil high in antioxidants, is generally safe for use. This is a phase 1 study, marking the first step in testing a new treatment in humans. Since curcumin and HP-EVOO are common dietary supplements, they are likely safe for most people. However, as this is early research, the full safety profile is still being determined. Researchers will closely monitor participants for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using curcumin with high phenolic extra virgin olive oil (HP-EVOO) for neurofibromatosis because it offers a natural alternative to traditional treatments like surgery and chemotherapy. Curcumin, a compound found in turmeric, is known for its anti-inflammatory and antioxidant properties, which might help manage the growth of tumors associated with neurofibromatosis. The addition of HP-EVOO enhances these effects due to its rich polyphenol content, potentially providing a dual-action approach that targets inflammation and oxidative stress. This combination could offer a less invasive and more holistic treatment option, sparking interest in its potential benefits.

What evidence suggests that this trial's treatments could be effective for neurofibromatosis?

Research has shown that curcumin, a natural substance in turmeric, might help treat brain diseases. Studies suggest it could reduce inflammation and stress in the body, both linked to tumor growth. In this trial, participants will receive a combination of curcumin and high phenolic extra virgin olive oil (HP-EVOO). This special olive oil is known for reducing inflammation, and when combined with curcumin, the effects might be stronger. Although direct evidence for its effect on neurofibromatosis is limited, curcumin and HP-EVOO offer a hopeful option to slow or stop tumor growth. ^{1 2 3 4 6}

Who Is on the Research Team?

Christopher Moertel

Principal Investigator

Masonic Cancer Center, Univeristy of Minnesota

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Neurofibromatosis (NF1) who have measurable skin neurofibromas. They must be able to give consent and not be on certain cancer drugs, immunosuppressants, or have swallowing issues that could affect taking the treatment. Pregnant individuals or those planning pregnancy during the study are excluded.

Inclusion Criteria

I have been diagnosed with NF1 through genetic testing or NIH criteria.

Voluntary signed written consent obtained before the performance of any study-related procedure not part of normal medical care

I have visible skin tumors due to neurofibromatosis.

Exclusion Criteria

Any comorbidities that may affect study participation in the judgement of enrolling investigator

Swallowing difficulties or strong gag reflex which may interfere with study compliance

Psychiatric illness, cognitive challenges, social situations, or other circumstances that would limit compliance with study requirements, per judgment of the enrolling investigator

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive curcumin and high phenolic extra virgin olive oil (HP-EVOO) twice a day for up to 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• curcumin
• high phenolic extra virgin olive oil (HP-EVOO)

Trial Overview The trial tests curcumin and high phenolic extra virgin olive oil (HP-EVOO) taken twice daily before meals for up to a year to see if they can help with NF1 symptoms. The only difference between participants is the dose of curcumin assigned when they join.

How Is the Trial Designed?

Group I: Curcumin with high phenolic extra virgin olive oil (HP-EVOO) Experimental Treatment 1 Intervention

Identical for all participants with the exception of the curcumin dose level, which is assigned at study enrollment.

curcumin is already approved in United States, European Union for the following indications:

Approved in United States as Curcumin for:

• Dietary supplement
• Not approved as a drug for specific medical conditions but used in clinical trials for various indications including neurofibromatosis type 1 (NF1)

Approved in European Union as Curcuma longa extract for:

• Dietary supplement
• Not approved as a drug for specific medical conditions but used in traditional medicine for various health benefits

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Published Research Related to This Trial

Curcumin-enriched virgin coconut oil (VCr) showed a significant 60% reduction in tumor incidence in mice with skin papillomas induced by DMBA, indicating its potential as a chemopreventive agent.

VCr also restored antioxidant levels in the skin, suggesting it enhances the body's defense against oxidative stress, although further research is needed to improve curcumin's bioavailability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin Enriched VCO Protects against 7,12-Dimethyl Benz[a] Anthracene-Induced Skin Papilloma in Mice. Narayanankutty, A., Nair, A., Illam, SP., et al.[2021]

Patients with Neurofibromatosis 1 (NF1) who followed a Mediterranean diet enriched with 1200 mg of curcumin daily showed a significant reduction in the number and volume of cutaneous neurofibromas after six months.

One patient experienced a notable 28% reduction in the volume of a large cranial plexiform neurofibroma, as confirmed by MRI, highlighting the potential of combining dietary approaches with curcumin for managing NF1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic Interplay between Curcumin and Polyphenol-Rich Foods in the Mediterranean Diet: Therapeutic Prospects for Neurofibromatosis 1 Patients. Esposito, T., Schettino, C., Polverino, P., et al.[2018]

Curcumin significantly inhibits the growth and migration of neuroblastoma (NB) cells (SK-N-SH), suggesting its potential as a therapeutic agent for this aggressive childhood cancer.

The mechanism of action involves inducing apoptosis through G2/M cell cycle arrest, activating caspase-3, and increasing reactive oxygen species (ROS), while also engaging p53 and Bcl-2 signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin induced G2/M cycle arrest in SK-N-SH neuroblastoma cells through the ROS-mediated p53 signaling pathway. Ye, Z., Chen, D., Zheng, R., et al.[2022]

Thymoquinone and curcumin demonstrated significant cytotoxic effects on neuroblastoma cell lines (NLF, NB69, and SK-N-BE(2)), indicating their potential as anti-cancer agents, with curcumin showing lower toxicity thresholds (IC50 values of 3.75-7.42 µM) compared to thymoquinone (IC50 values of 5.16-16.3 µM).

Both compounds not only reduced cell proliferation but also increased apoptosis rates in neuroblastoma cells, suggesting they could be promising therapeutic options for high-risk neuroblastoma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumoral Effects of Curcumin (Curcuma longa L.) and Thymoquinone (Nigella sativa L.) on Neuroblastoma Cell Lines. Korff, JM., Menke, K., Schwermer, M., et al.[2021]

Colorectal cancer (CRC) is significantly influenced by lifestyle factors, with a high incidence in the U.S. (52/100,000) compared to much lower rates in India (7/100,000), suggesting that diet and lifestyle play a crucial role in its development.

Nutraceuticals such as curcumin, thymoquinone, and others have shown promise in both preventing and treating CRC by targeting multiple biological pathways, making them a safe and affordable alternative to traditional pharmaceuticals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention and Treatment of Colorectal Cancer by Natural Agents From Mother Nature. Aggarwal, B., Prasad, S., Sung, B., et al.[2022]

Curcumol, a major component of the Chinese medicinal herb Curcuma phaeocaulis, significantly inhibits neurite outgrowth and cell proliferation in differentiated PC12 cells without causing cell death, indicating potential developmental neurotoxicity.

The study suggests that curcumol induces oxidative stress and represses the NCAM/FAK signaling pathway, which may be responsible for its inhibitory effects on neurite outgrowth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An investigation of the developmental neurotoxic potential of curcumol in PC12 cells. Yu, C., Sun, X., Niu, Y.[2017]

Topical application of nutraceuticals, particularly turmeric, before exposure to croton oil significantly reduced skin tumor incidence and delayed tumor formation in a study using dimethylbenz[a]anthracene (DMBA) to initiate tumors, with turmeric showing a 30% tumor incidence and an 87.2% decrease in tumors.

The most effective treatment protocol involved applying the nutraceuticals one hour before croton oil, as opposed to other timing methods, highlighting the importance of application timing in maximizing protective effects against skin tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative potencies of nutraceuticals in chemically induced skin tumor prevention. Villaseñor, IM., Simon, MK., Villanueva, AM.[2006]

A Phase I clinical trial involving 9 healthy volunteers demonstrated that turmeric oil (TO) is safe and well-tolerated over a 3-month period, with no significant adverse effects on blood pressure, weight, or organ function.

Despite some participants experiencing mild allergic reactions or intercurrent illnesses, the majority completed the study without any clinical, hematological, or hepatic toxicity, supporting the potential for TO to be further tested in patients with precancerous conditions like oral submucous fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early human safety study of turmeric oil (Curcuma longa oil) administered orally in healthy volunteers. Joshi, J., Ghaisas, S., Vaidya, A., et al.[2013]

Combining curcumin with BM-ANF1 significantly inhibits the growth of colon cancer cells (HCT-116) more effectively than using either compound alone, suggesting a synergistic effect in cancer treatment.

The combination therapy works by promoting apoptosis and cell cycle arrest, while also altering key signaling pathways, including the downregulation of growth factors and upregulation of tumor suppressors, indicating a robust mechanism of action against colon cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Curcumin synergizes the growth inhibitory properties of Indian toad (Bufo melanostictus Schneider) skin-derived factor (BM-ANF1) in HCT-116 colon cancer cells. Giri, B., Gomes, A., Sengupta, R., et al.[2013]

In silico studies identified five dietary compounds that are stronger inhibitors of the DYRK2 target (5ZTN) than curcumin, suggesting potential new avenues for neuroblastoma treatment.

In vitro studies showed that caffeic acid has anti-proliferative effects on tumor cells (U87) while potentially benefiting normal brain cells (NHA), indicating a need for careful evaluation of compounds for safety and efficacy in treating neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential Benefits of Dietary Plant Compounds on Normal and Tumor Brain Cells in Humans: In Silico and In Vitro Approaches. Pirvu, LC., Neagu, G., Albulescu, A., et al.[2023]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-08561

Curcumin and High Phenolic Extra Virgin Olive Oil for ... This phase I study evaluates the safety and best dose of curcumin and high phenolic extra virgin olive oil for slowing or stopping the growth of tumors

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05363267

NCT05363267 | NF-1, Nutraceutical Intervention Curcumin and high phenolic extra virgin olive oil (HP-EVOO) may continue for up to 12 months in the absence of unacceptable side effects. Official Title. Study ...

3. withpower.com withpower.com/trial/phase-1-neurofibromatosis-1-6-2022-cb5f2

Nutraceuticals for Neurofibromatosis · Info for Participants This trial involves taking curcumin and a special type of olive oil twice a day to help reduce inflammation and oxidative stress.

4. sciencedirect.com sciencedirect.com/science/article/pii/S0734975025000540

Application of curcuminoids in inflammatory, ... Curcumin, a natural compound found in turmeric, has shown promise in treating brain-related diseases and conditions associated with aging.

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05363267/nf-1-nutraceutical-intervention

NF-1, Nutraceutical Intervention | Clinical Research Trial ... Treatment with high phenolic olive oil or curcumin within six months of study entry. Known pregnancy or anticipated conception during the 1 year ...

6. ctv.veeva.com ctv.veeva.com/study/nf-1-nutraceutical-intervention

NF-1, Nutraceutical Intervention - ClinicalTrials.Veeva Curcumin and high phenolic extra virgin olive oil (HP-EVOO) may continue for up to 12 months in the absence of unacceptable side effects.