NF-1, Nutraceutical Intervention

Study Overview
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Brief Summary
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The treatment plan is identical for all participants with the exception of the curcumin dose level that is assigned at study enrollment. Participants are instructed to take the curcumin and olive oil one after the other (order does not matter) twice a day on an empty stomach ideally 30 minutes before breakfast and dinner. 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
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Study of Nutraceutical Intervention With High Phenolic Extra Virgin Olive Oil and Curcumin for Neurofibromatosis, Type 1 (NF1)

Conditions
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Neurofibromatosis 1

Intervention / Treatment
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* Dietary Supplement: curcumin, high phenolic extra virgin olive oil (HP-EVOO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NF1 diagnosis based on NIH Consensus Conference Criteria and/or genetic testing Measurable cutaneous neurofibromas (cNFs) with or without plexiform NF Aged 18 years or older at the time of written consent Voluntary signed written consent obtained before the performance of any study-related procedure not part of normal medical care Exclusion Criteria: Concurrent treatment with selumetinib or other MAPK, MEK or mTOR inhibitors, other targeted therapies, chemotherapy or radiation Conditions requiring systemic immunosuppression Swallowing difficulties or strong gag reflex which may interfere with study compliance Any comorbidities that may affect study participation in the judgement of enrolling investigator Psychiatric illness, cognitive challenges, social situations, or other circumstances that would limit compliance with study requirements, per judgment of the enrolling investigator Treatment with high phenolic olive oil or curcumin within six months of study entry Known pregnancy or anticipated conception during the 1 year study period

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Curcumin with high phenolic extra virgin olive oil (HP-EVOO)<br>Identical for all participants with the exception of the curcumin dose level, which is assigned at study enrollment. | Dietary Supplement: curcumin, high phenolic extra virgin olive oil (HP-EVOO)<br>* identical for all participants with the exception of the curcumin dose level Dose 1: 1000 mg Curcumin daily dose with 1 capsule of 25 ml HP-EVOO volume at morning and night Dose 1: 2000 mg Curcumin daily dose with 2 capsules of 25 ml HP-EVOO volume at morning and night Dose 3: 4000 mg Curcumin daily dose with 4 capsules of 25 ml HP-EVOO volume at morning and night<br>* Other names: high phenolic extra virgin olive oil (HP-EVOO);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary objective of this study is to establish the safety and preliminary activity of curcumin and oleocanthal-rich olive oil supplementation in adult NF-1 persons with cutaneous neurofibromas. | The safety of this supplementation will be measured by the incidence of unacceptable/dose limiting toxicity (DLT) as defined any new Grade 2 or greater toxicity (based on CTCAE v 5). | End of treatment (12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize the toxicities associated with the planned intervention | Incidence of unacceptable/dose limiting toxicity defined as any new ≥Grade 2 toxicity (based on CTCAE v 5) that cannot be attributed to the disease under treatment or other reason. | 4 weeks after 1st dose of curcumin | 
| To evaluate the effect of the intervention on BMI | The BMI will be measures across dose level group 95% confidence intervals. | End of Treatment (12 months) | 
| To evaluate the effect of the intervention on lipid panel | The lipid panel will be measures across dose level group 95% confidence intervals. | End of Treatment (12 months) | 
| To assess the effect of the intervention on quality of life | Focused on skin related morbidity and pain will be evaluated using the average and range of SkinDex scale (0-100) | End of treatment (12 months) | 
| To determine preliminary efficacy of the intervention | Measure the volumetric measurement of target plexiform neurofibroma (% difference from baseline will be reported) | End of treatment (12 months) | 
| To identify issues with compliance to the planned intervention | Incidence of study deviations | End of treatment (12 months) |