Evaluating Mitochondrial Dysfunction in Patients With Neurofibromatosis Type 1

Study Overview
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Brief Summary
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Neurofibromatosis type 1 is a common genetic disease with a broad spectrum of clinical manifestations in multiple organs of the body. This project will study the (dys)function of mitochondria in patients with neurofibromatosis through multiple collections of blood samples from patients and people not afflicted by neurofibromatosis (control group). This study will evaluate how the function of mitochondria changes with time and if medications and supplements can influence the function of the mitochondria. Patients will also answer questions regarding symptoms like fatigue and pain.

Detailed Description
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Neurofibromatosis type 1 is a common genetic disease with a broad spectrum of clinical manifestations in multiple organs of the body. Some of those symptoms are skin lesions, tumors and cancers, as also pain, and fatigue. In animal models of this disease, dysfunction of mitochondria, a part of the cell which is responsible for energy production, is often described. This project will study the (dys)function of mitochondria in patients with neurofibromatosis through multiple collections of blood samples from patients and people not afflicted by neurofibromatosis (control group). Those blood samples will be used to run tests that analyses the function of the mitochondria and compare the results from the neurofibromatosis group with the control group. As multiple samples from the same patient will be tested in different times, this study will evaluate how the function of mitochondria changes with time and if medications and supplements can influence the function of the mitochondria. Patients will also answer questions regarding symptoms like fatigue and pain. Doing so, the investigator plan to confirm mitochondrial dysfunction in patients, if the degree of dysfunction correlates with symptoms like pain and fatigue, and if supplements and medication like MEK inhibitors that patients with neurofibromatosis type 1 use in a daily basis modulates (for better or worse) a pre-existing mitochondrial dysfunction.

Official Title
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Evaluating Mitochondrial Dysfunction in Patients With Neurofibromatosis Type 1

Conditions
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Neurofibromatosis 1

Intervention / Treatment
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* Diagnostic Test: Blood draw
* Other: FACIT-F and Pain Scales


Participation Criteria
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Eligibility Criteria
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NF1 Group: Inclusion Criteria: Diagnosed with NF1 Inclusion Criteria: Not the first degree relative (biological parent, sibling, or child) of the NF1 patient who is in the NF1 group

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| NF1 Group<br>This study will look to enroll 40 to 45 adults over 18 years old diagnosed with NF1. | Diagnostic Test: Blood draw<br>* • An additional 10 mL of blood will then be drawn for mitochondrial testing purposes.<br>Other: FACIT-F and Pain Scales<br>* • Questionnaires regarding pain and fatigue will be provided for the subject to review and answer.<br>|
| Control Group<br>This study will look to enroll 10 to 15 adults over 18 years old without NF1. | Diagnostic Test: Blood draw<br>* • An additional 10 mL of blood will then be drawn for mitochondrial testing purposes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrate that mitochondrial respiration efficiency of PBMCs inversely correlates with clinical symptoms of NF1 patients. | Mitochondrial function and cellular bioenergetics will be measured in PBMCs and platelets isolated from blood. Clinical repercussions of MD in NF1 will be measured through serial scores of fatigue and pain on the same days that PBMC and platelets are collected. Fatigue will be assessed through the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). | 1 year | 
| Measure the change over time of therapeutic interventions impact on mitochondrial function and metabolic plasticity of circulating cells of NF1 patients. | The NF1 and healthy control groups' mitochondrial function and metabolic plasticity parameters will be compared in addition to longitudinal changes in these parameters for each NF1 patient. Linear regression analysis will be utilized to establish the relationship between coupling efficiency, respiratory capacity (ATP-linked, reserve capacity etc.) as well as metabolic plasticity and NF1 clinical phenotype and biochemical scores for fatigue, pain, CK, cardiac function, BMI, and liver function. Analysis of variance for repeated measures will also be used to analyze changes in these parameters over time by each group (NF1 patients before and after Vitamin D and/or KOS administration). | Completed at each of the 3 total visits required by the study. Each visit will occur at 14 weeks (+/- 2 weeks) |