Trial Summary
What is the purpose of this trial?This trial involves taking curcumin and a special type of olive oil twice a day to help reduce inflammation and oxidative stress. It targets individuals who can tolerate this treatment for an extended period. Curcumin is a natural polyphenol known for its antioxidant and anti-inflammatory properties, and it has been studied in various contexts including metabolic syndrome, diabetes, and exercise-induced oxidative stress.
What safety data exists for nutraceuticals used in neurofibromatosis treatment?Turmeric and its extracts, such as curcumin, have been used safely for centuries as a spice and remedy. A Phase I clinical trial showed turmeric oil is safe and well-tolerated in humans over 3 months. Curcumin, a component of turmeric, has no discernable toxicity and is known for its anticancer properties, though its bioavailability is limited. Curcumol, another compound from a related plant, may have developmental neurotoxic potential, but this is not directly related to turmeric or curcumin. Overall, turmeric and curcumin are considered safe based on historical use and early human studies.12357
Is curcumin and high phenolic extra virgin olive oil a promising treatment for Neurofibromatosis?Yes, curcumin combined with a Mediterranean diet rich in polyphenols, like high phenolic extra virgin olive oil, shows promise in reducing the size and number of neurofibromas in Neurofibromatosis patients.346810
What data supports the idea that Nutraceuticals for Neurofibromatosis is an effective treatment?The available research shows that a Mediterranean diet enriched with curcumin led to a significant reduction in the number and size of skin tumors in Neurofibromatosis 1 patients. One patient even experienced a 28% reduction in a large tumor, as confirmed by imaging. This suggests that combining curcumin with a specific diet may help manage the condition.368910
Do I need to stop my current medications to join the trial?The trial does not specify if you need to stop taking your current medications, but you cannot be on selumetinib, MAPK, MEK, or mTOR inhibitors, or other targeted therapies, chemotherapy, or radiation.
Eligibility Criteria
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 am 18 years old or older.
I have been diagnosed with NF1 through genetic testing or NIH criteria.
I have visible skin tumors due to neurofibromatosis.
Exclusion Criteria
I am not currently on treatments like selumetinib, MAPK, MEK, mTOR inhibitors, other targeted therapies, chemotherapy, or radiation.
I am on medication that weakens my immune system.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: Curcumin with high phenolic extra virgin olive oil (HP-EVOO)Experimental Treatment1 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:
๐บ๐ธ 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)
๐ช๐บ 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
Find a clinic near you
Research locations nearbySelect from list below to view details:
Masonic Cancer Center, University of MinnesotaMinneapolis, MN
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Who is running the clinical trial?
Masonic Cancer Center, University of MinnesotaLead Sponsor
References
Comparative potencies of nutraceuticals in chemically induced skin tumor prevention. [2006]Four nutraceuticals, sugar beet roots, cucumber fruits, New Zealand spinach leaves, and turmeric rhizomes, were evaluated for their comparative effectiveness against dimethylbenz[a]anthracene (DMBA)-initiated and croton oil-promoted skin tumors. Three different protocols were used. The most effective protocol (Protocol 2) is the topical application of the nutraceuticals 1 h before croton oil. There was a decrease in the percent skin tumor incidence, a decrease in multiplicity of skin tumors, and a later onset of skin tumors compared with the positive control for all the nutraceuticals tested, with turmeric being the most potent, as evidenced by 30% skin tumor incidence, 87.2% decrease in skin tumors, and a 5-wk delay in skin tumor formation compared with the positive control. Topical application of the nutraceuticals daily for 5 days before DMBA and 1 h before croton oil (Protocol 1) and immediately after croton oil (Protocol 3) did not have an additional protective effect against skin tumors compared with Protocol 2. Kruskal-Wallis analysis of variance by ranks showed that Protocol 2 is the most effective, with the treatment groups belonging to different populations at the 0.05 level of significance compared with alpha = 0.20 for Protocols 1 and 3. Turmeric is the most potent nutraceutical, because the average number of tumors formed after application of tumeric is statistically different from the positive control at alpha = 0.01.
Early human safety study of turmeric oil (Curcuma longa oil) administered orally in healthy volunteers. [2013]Turmeric extract and turmeric oil have shown chemoprotective effect against chemically-induced malignancies in experimental animals. They can reverse precancerous changes in oral submucous fibrosis in humans. The use of turmeric or Curcuma longa Linn as a spice and household remedy has been known to be safe for centuries. In view of the long term administration required for cancer prevention a Phase I clinical trial of turmeric oil (TO) was designed to study the safety and tolerance of TO in volunteers for a period of 3 months.
Curcumin synergizes the growth inhibitory properties of Indian toad (Bufo melanostictus Schneider) skin-derived factor (BM-ANF1) in HCT-116 colon cancer cells. [2013]Curcumin, an active ingredient of turmeric with no discernable toxicity, inhibits the growth of transformed cells and the development and progression of colon carcinogenesis in experimental animals. Recent data from one of our laboratories demonstrated that a crude skin extract or a purified crystalline compound (Bufo melanostictus-antineoplastic factor 1, BM-ANF1) from Indian common toad (Bufo melanostictus, Schneider) skin inhibits the growth of human leukemic cells. The present investigation was undertaken to determine whether combining BM-ANF1 with curcumin would be a better therapeutic strategy for colon cancer.
Prevention and Treatment of Colorectal Cancer by Natural Agents From Mother Nature. [2022]Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States after cancers of the lung and the breast/prostate. While the incidence of CRC in the United States is among the highest in the world (approximately 52/100,000), its incidence in countries in India is among the lowest (approximately 7/100,000), suggesting that lifestyle factors may play a role in development of the disease. Whereas obesity, excessive alcohol consumption, a high-calorie diet, and a lack of physical activity promote this cancer, evidence indicates that foods containing folates, selenium, Vitamin D, dietary fiber, garlic, milk, calcium, spices, vegetables, and fruits are protective against CRC in humans. Numerous agents from "mother nature" (also called "nutraceuticals,") that have potential to both prevent and treat CRC have been identified. The most significant discoveries relate to compounds such as cardamonin, celastrol, curcumin, deguelin, diosgenin, thymoquinone, tocotrienol, ursolic acid, and zerumbone. Unlike pharmaceutical drugs, these agents modulate multiple targets, including transcription factors, growth factors, tumor cell survival factors, inflammatory pathways, and invasion and angiogenesis linked closely to CRC. We describe the potential of these dietary agents to suppress the growth of human CRC cells in culture and to inhibit tumor growth in animal models. We also describe clinical trials in which these agents have been tested for efficacy in humans. Because of their safety and affordability, these nutraceuticals provide a novel opportunity for treatment of CRC, an "old age" disease with an "age old" solution.
An investigation of the developmental neurotoxic potential of curcumol in PC12 cells. [2017]Curcuma phaeocaulis Val. is a Chinese medicinal herb that is contraindicated during pregnancy for over a thousand years in China. The aims of the present study were to evaluate the effect of curcumol (one of the major components of C. phaeocaulis Val.) on neurite outgrowth and characterize the signal transduction pathways in PC12 cells. Curcumol significantly inhibited neurite outgrowth and cell proliferation, but did not cause cell death at a concentration of 450 ฮผM in differentiated PC12 cells. In addition, curcumol evoked oxidative stress and it was indicated by an elevation in reactive oxygen species (ROS) and lipid peroxidation (LPO). Although PC12 cells exhibited inhibition of the differentiation into the acetylcholine (ACh) phenotype following 450 ฮผM curcumol exposure, there was no significant alteration in net shift toward the ACh phenotype or tyrosine hydroxylase (TH) phenotype was observed. Neural cell adhesion molecule (NCAM)/focal adhesion kinase (FAK) but not extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling was repressed by curcumol exposure in differentiated PC12 cells. Curcumol does not affect calpain activity and nuclear factor-ฮบB (NF-ฮบB) DNA-binding activity. These findings suggest that curcumol might be a developmental neurotoxicant and NCAM/FAK signaling pathway may play an important role in curcumol-evoked inhibition of neurite outgrowth.
Synergistic Interplay between Curcumin and Polyphenol-Rich Foods in the Mediterranean Diet: Therapeutic Prospects for Neurofibromatosis 1 Patients. [2018]Neurofibromas are the hallmark lesions in Neurofibromatosis 1 (NF1); these tumors are classified as cutaneous, subcutaneous and plexiform. In contrast to cutaneous and subcutaneous neurofibromas, plexiform neurofibromas can grow quickly and progress to malignancy. Curcumin, a turmeric-derived polyphenol, has been shown to interact with several molecular targets implicated in carcinogenesis. Here, we describe the impact of different dietary patterns, namely Mediterranean diet (MedDiet) compared to the Western diet (WesDiet), both with or without curcumin, on NF1 patients' health. After six months, patients adopting a traditional MedDiet enriched with 1200 mg curcumin per day (MedDietCurcumin) presented a significant reduction in the number and volume of cutaneous neurofibromas; these results were confirmed in subsequent evaluations. Notably, in one patient, a large cranial plexiform neurofibroma exhibited a reduction in volume (28%) confirmed by Magnetic Resonance Imaging. Conversely, neither unenriched MedDiet nor WesDiet enriched with curcumin exhibited any significant positive effect. We hypothesize that the combination of a polyphenol-rich Mediterranean diet and curcumin was responsible for the beneficial effect observed on NF1. This is, to the best of our knowledge, the first experience with curcumin supplementation in NF1 patients. Our report suggests that an integrated nutritional approach may effectively aid in the management of NF1.
Curcumin Enriched VCO Protects against 7,12-Dimethyl Benz[a] Anthracene-Induced Skin Papilloma in Mice. [2021]Virgin coconut oil (VCO) and turmeric are traditionally being used in Indian cuisine systems; VCO is a natural combination of medium-chain triglyceride and polyphenols with established pharmacological potential. Curcumin isolated from turmeric is renowned for its anticancer properties, however, with limited clinical success due to poor bioavailability. Considering the lipophilic nature of VCO, curcumin added to VCO is expected to have synergistic/additive actions. In this study, the chemopreventive potential of curcumin enriched VCO (VCr) (4 and 8 mL/Kg orally) was analyzed in 7,12-dimethyl benz[a]anthracene (DMBA;470 nmoles/200 µL/week for two weeks topical)/croton oil (3% v/v in 200 µL acetone twice a week for 6 weeks topical) induced skin papilloma. In DMBA control animals, an average incidence of 13 papilloma/mice (latency period of 11.6 ± 1.5 weeks) was recorded. Pretreatment with VCrH (8 mL/kg) had a 60% inhibition of tumor index, and an increased latency period (12.5 ± 0.9 weeks). Additionally, DMBA/croton oil-induced reduction in glutathione levels and concomitant increase in thiobarbituric acid reactive substance (TBARS) in the skin microenvironment were restored by VCr. The study thus suggests that the VCr promotes antioxidant status in vivo and imparts an improved anticarcinogenic potential. However, further studies are necessary to ascertain the improvement in bioavailability of curcumin .
Antitumoral Effects of Curcumin (Curcuma longa L.) and Thymoquinone (Nigella sativa L.) on Neuroblastoma Cell Lines. [2021]Overall survival of high-risk neuroblastoma patients is still poor, emphasizing the need for novel therapeutic options. There is evidence for anti-cancer properties of the herbal substances thymoquinone and curcumin. These substances are isolated from Nigella sativa L. and Curcuma longa L., respectively, which are used in traditional medicine.
Curcumin induced G2/M cycle arrest in SK-N-SH neuroblastoma cells through the ROS-mediated p53 signaling pathway. [2022]Neuroblastoma (NB) is a solid tumor in the nervous system and has a high mortality rate in children. Curcumin has well-characterized anticancer properties, while there is no effective method in clinical treatment. MTT assays revealed that curcumin dramatically inhibited the proliferation of SK-N-SH cells. Compared with the control group, curcumin markedly restrained the migration of SK-N-SH cells. Curcumin induced SK-N-SH cell apoptosis by G2/M cycle arrest and activated caspase-3 activity. Furthermore, curcumin promoted the overproduction of intracellular ROS and apoptosis induced by activating p53 and Bcl-2 signal pathways. This finding demonstrated the application of curcumin is an effective strategy for the therapeutics of NB.
Potential Benefits of Dietary Plant Compounds on Normal and Tumor Brain Cells in Humans: In Silico and In Vitro Approaches. [2023]Neuroblastoma can be accessed with compounds of larger sizes and wider polarities, which do not usually cross the blood-brain barrier. Clinical data indicate cases of spontaneous regression of neuroblastoma, suggesting a reversible point in the course of cell brain tumorigenesis. Dual specificity tyrosine-phosphorylation-regulated kinase2 (DYRK2) is a major molecular target in tumorigenesis, while curcumin was revealed to be a strong inhibitor of DYRK2 (PBD ID: 5ZTN). Methods: in silico studies by CLC Drug Discovery Workbench (CLC) and Molegro Virtual Docker (MVD) Software on 20 vegetal compounds from the human diet tested on 5ZTN against the native ligand curcumin, in comparison with anemonin. In vitro studies were conducted on two ethanolic extracts from Anemone nemorosa tested on normal and tumor human brain cell lines NHA and U87, compared with four phenolic acids (caffeic, ferulic, gentisic, and para-aminobenzoic/PABA). Conclusions: in silico studies revealed five dietary compounds (verbascoside, lariciresinol, pinoresinol, medioresinol, matairesinol) acting as stronger inhibitors of 5ZTN compared to the native ligand curcumin. In vitro studies indicated that caffeic acid has certain anti-proliferative effects on U87 and small benefits on NHA viability. A. nemorosa extracts indicated potential benefits on NHA viability, and likely dangerous effects on U87.