Evaluating Mitochondrial Dysfunction in Patients With Neurofibromatosis Type 1

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.

Study Overview

• Status: Recruiting
• Conditions: Neurofibromatosis 1
• Intervention / Treatment: Diagnostic test: Blood draw; Other: FACIT-F and Pain Scales

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Aaron Holley; Phone Number: 501-686-8274; Email: jaholley@uams.edu
• Study Contact Backup: Name: Beth Scanlan; Phone Number: 501-686-8274; Email: bscanlan@uams.edu

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences
      • Principal Investigator: Erika Santos Horta, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

• Patients with NF1 at the UAMS Adult NF1 clinic will be invited to participate in the study during their regular clinic appointments.
• Spouses, friends, and non-relatives of NF1 patients who come to the UAMS Adult NF1 Clinic will be invited to participate in the control arm of the study at the time of the patient appointment.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Arkansas
• Investigators: Principal Investigator: Erika Santos Horta, MD, University of Arkansas

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2023
• Primary Completion (Estimated): July 1, 2025
• Study Completion (Estimated): July 1, 2026

Study Registration Dates

• First Submitted: May 31, 2023
• First Submitted That Met QC Criteria: June 12, 2023
• First Posted (Actual): June 22, 2023

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Genetic Diseases, Inborn; Neuromuscular Diseases; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Neoplastic Syndromes, Hereditary; Nerve Sheath Neoplasms; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma
• Other Study ID Numbers: 274877

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No