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: Completed
• 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 (Actual): 55

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences

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
Mitochondrial Respiration Efficiency (as Measured by OCR).	Mitochondrial respiration efficiency is measured here by the oxygen consumption rate (OCR) which is measured in units of picomoles per minute.	Baseline, Week 14, Week 28
Mitochondrial Respiration Efficiency (as Measured by ECAR).	Mitochondrial respiration efficiency is measured here by the extracellular acidification rate (ECAR) which is measured in millipH per minute.	Baseline, Week 14, Week 28
Vitamin D Levels	We hypothesize that mitochondrial dysfunction among NF1 patients sensitizes them to therapeutic interventions targeting mitochondria. We will assess the impact of vitamin D treatment to potentially improve mitochondrial function as measured by OCR. Vitamin D is measured in units of nanogram per milliliter.	Baseline
Pain (as Measured With NRS-11 for Current Pain Over the Past 24 Hours) of NF1 Patients	The NF1 clinical symptom of pain as measured with The Numeric Pain Rating Scale (NRS-11) for current pain over the past 24 hours (min=0, max=10, higher score = more pain). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits).	Baseline, Week 14, Week 28
Pain (as Measured With NRS-11 for Best Pain Over the Past 24 Hours) of NF1 Patients	The NF1 clinical symptom of pain as measured with The Numeric Pain Rating Scale (NRS-11) for best pain over the past 24 hours (min=0, max=10, higher score = more pain). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits).	Baseline, Week 14, Week 28
Pain (as Measured With NRS-11 for Worst Pain Over the Past 24 Hours) of NF1 Patients	The NF1 clinical symptom of pain as measured with The Numeric Pain Rating Scale (NRS-11) for worst pain over the past 24 hours (min=0, max=10, higher score = more pain). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits).	Baseline, Week 14, Week 28
Fatigue (as Measured FACIT-F TOI) of NF1 Patients.	The NF1 clinical symptom of fatigue as measured with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F). This is done in 3 visits spanning 28 weeks (14 weeks plus or minus 2 days between visits). The FACIT-F asks respondents to rate items on a scale from 0 to 4. There are 5 subscales with varying possible ranges (due to varying numbers of items) as follows: Physical Well-Being Subscale: Range 0-28,; Social/Family Well-Being Subscale: Range 0-28,; Emotional Well-Being Subscale: Range 0-24,; Functional Well-Being Subscale: Range 0-28, and; Fatigue Subscale: Range 0-52. The Trial Outcome Index (TOI) is the total score we chose to analyze. It consists of the sum of the Physical Well-Being Subscale, Functional Well-Being Subscale, and Fatigue Subscale and has a score range of 0-108. The higher the score, the better the quality of life.	Baseline, Week 14, Week 28

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 (Actual): August 23, 2024
• Study Completion (Actual): August 23, 2024

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): May 8, 2025
• Last Update Submitted That Met QC Criteria: April 21, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Genetic Diseases, Inborn; Metabolic Diseases; Peripheral Nervous System Diseases; Neoplasms by Histologic Type; Neurodegenerative Diseases; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Heredodegenerative Disorders, Nervous System; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Peripheral Nervous System Neoplasms; Neurofibromatoses; Neurofibromatosis 1; Neurofibroma; Mitochondrial Diseases
• 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
• product manufactured in and exported from the U.S.: No