A Study to Evaluate the Feasibility of a Physiologic Biomarker to Assess Pain and Other Sensory Problems Using Pupillometry in Participants With Neurofibromatosis Type 1 (NF1)

Background:

Neurofibromatosis type 1 (NF1) is a genetic condition that causes tumors to grow along the nerves in the skin, brain, and other parts of the body. People with NF1 often have pain and may experience other abnormal sensations like itching, numbness, or tingling. These symptoms can affect their daily life. Researchers want to learn more about these symptoms and find better ways to measure pain in people with NF1.

Objective:

To learn if a device called the AlgometRx Nociometer(Registered trademark) is effective in measuring pain or other abnormal sensations in people with NF1.

Eligibility:

People aged 1 year and older with NF1.

Design:

Individuals can have up to 3 assessments completed in person. Each assessment may last up to 1.0 to 1.5 hours.

Individuals will be screened. They will complete questionnaires about their health and how bad their pain is. If participants are having blood drawn for other reasons, some additional samples may be used in this study.

The AlgometRx Nociometer includes an electrode that will be placed onto a finger or a toe. The electrode will send non-painful electrical signals to activate nerves in the finger or toe. At the same time, a camera will be used to record changes in the pupil of the eye. The test will be done on all 4 of the participant s limbs; however, researchers may skip 1 or more limbs for various reasons. This test takes about 10 seconds to complete with at least a one-minute rest between testing different limbs.

Individuals will be asked to do a 2nd assessment with the AlgometRx Nociometer that may be done 1 hour later but no more than 72 hours after the first assessment. Participants who will be returning for another visit can opt to do a 3rd assessment that will be done at least 4 weeks but not more than 18 months after the 1st....

Study Overview

• Status: Recruiting
• Conditions: Neurofibromatosis Type 1
• Intervention / Treatment: Device: AlgometRx Nociometer

Detailed Description

Background:

• Chronic pain is a common and often debilitating symptom of neurofibromatosis 1 (NF1) that is related to multiple tumor (e.g., plexiform neurofibromas; PN) and non-tumor (e.g., headaches) manifestations.
• Patient-reported outcome (PRO) measures have been used to assess pain in PN trials; however, few are validated for NF populations. In addition, the subjective measurement of pain symptoms can be difficult particularly in young children, those with learning disabilities, and due to patients having various types of NF-related pain and other sensory problems.
• There is a critical unmet need for a simple, non-invasive, and objective measure of pain and other sensory problems for individuals with NF1.
• AlgometRx Nociometer (Registered Trademark) is a novel integration of infrared video pupillometry and neuroselective stimulation, and the outcome measure obtained from an assessment with this device is the Neuropathy Index. The use of the AlgometRx Nociometer (Registered Trademark) in studies was determined to be non-significant risk (NSR) by the Children s National Hospital (CNH) Institutional Review Board (IRB) based on similar technologies that have been defined by the Food and Drug Administration (FDA) to be NSR.
• In addition to the early detection and targeted clinical management and monitoring of pain and nociceptive processing in patients with NF1, this device also may help us learn more about the underlying mechanisms of their pain, as well as their symptoms of numbness and tingling (paresthesia), muscle weakness, loss of reflexes/hyperreflexia, and altered sensation.
• This novel biomarker could fill a critical gap for an objective, simple, and sensitive assessment to quantify and monitor NF-related pain as a physiologic measure for clinical monitoring and as potential surrogate marker for response in treatment trials.

Objective:

-To describe the feasibility of using the AlgometRx Nociometer (Registered Trademark) device to conduct a physiologic assessment of pain in different age groups of participants with NF1.

Eligibility:

• Participants must have a history of clinical or genetic diagnosis of NF1
• Age >= 1 year
• At least one eye with an intact pupillary reflex
• At least one digit (finger or toe) without open wounds for application of the device
• Must understand English or Spanish
• Participants who are < 18 years must have a caregiver willing to help the child engage in study procedures, assist with fitting the AlgometRx Nociometer (Registered Trademark) device, and complete the observer reported (ObsRO) measures. Note: the caregiver of a child participant >= 5 years old must be able to understand English or Spanish, the caregiver of a child participant 1-4 years old must be able to understand English (to help complete the observational pain measure for the younger children that is only available in English).

Design:

• The design will be a multi-site diagnostic pilot study to describe the feasibility and acceptability and to evaluate the initial psychometric properties (reliability, validity, sensitivity to change) of a novel objective pain measurement device [AlgometRx Nociometer (Registered Trademark)] for use in future clinical trials for participants with NF1. NCI is the lead site and Children's National Hospital (CNH) is the participating site; both sites will enroll participants with NF1 in this study.
• A cross-sectional design will be used to describe the acceptability of the assessment with the AlgometRx Nociometer (Registered Trademark) device as well as construct validity of the Neuropathy Index. A longitudinal design will be used to assess test-retest reliability and sensitivity to change of the Neuropathy Index.
• The sample will consist of 55 evaluable participants who will be placed into 5 cohorts defined by age (1-4; 5-7; 8-12; 13-17; >= 18 years) with approximately 11 participants in each group (plus/minus 3) and total enrollment of 70 participants.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pamela L Wolters, Ph.D.; Phone Number: (240) 760-6035; Email: woltersp@mail.nih.gov

Study Locations

• United States
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Recruiting
      • Children's National Medical Center
      • Contact: Julia Finkel, M.D.; Phone Number: 202-476-4867; Email: jfinkel@cnmc.org
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: National Cancer Institute Referral Office; Phone Number: 888-624-1937; Email: NCIMO_Referrals@mail.nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:
• History of clinical or genetic diagnosis of NF1 as per the 2021 revised diagnostic criteria
• Age >= 1 year
• At least one digit (finger or toe) without open wounds for application of the device
• Individuals must understand English or Spanish
• Individuals who are < 18 years must have a caregiver willing to help the child engage in study procedures, assist with fitting the AlgometRx Nociometer (Registered Trademark) device, and complete the observer reported (ObsRO) measures. Note: the caregiver of a child participant >= 5 years old must be able to understand English or Spanish, the caregiver of a child participant 1-4 years old must be able to understand English (to help complete the observational pain measure for the younger children that is only available in English)
• Ability of individual or parent/guardian to understand and the willingness to sign a written informed consent document

EXCLUSION CRITERIA

• History of eye pathology which precludes pupillometry, such as problems with pupillary reflex, blindness or inability to open at least one eye fully for evaluation
• Individuals with chronic use of medication that specifically affects their pupillary response, such as atropine-containing eye drops
• Uncontrolled intercurrent illness evaluated by medical history that would potentially increase the risk to the participant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1/Feasibility and longitudinal assessments; Evaluation with the AlgometRx device and patient- and observer-reported outcome measures	Device: AlgometRx Nociometer; Novel objective pain measurement device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the feasibility of using AlgometRx Nociometer device in different age groups	Proportion of individuals who successfully complete the AlgometRx Nociometer assessment by each of the five age stratified groups (1-4, 5-7, 8-12, 13-17, 18+ years). This analysis will be performed on the Feasibility Analysis Data Set. Successful completion rate for each age group.	Baseline (enrollment, Time 1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Describe the acceptability of the physiologic pain assessment using the AlgometRx Nociometer device in different age groups	Acceptability will be described per age group for the three questions on the Acceptability Questionnaire.	Time 1
Evaluate the test-retest reliability of the physiologic pain measure (Neuropathy Index)	Test-retest reliability will be measured by the intraclass correlation coefficient in participants with stable pain.	Time 1, repeated 1-72 hours later (Time 2)
Evaluate the construct validity of the physiologic pain measure (Neuropathy Index)	Convergent and discriminant validity with the PRO/ObsRO measures will be measured through parametric (Pearson s) or nonparametric (Spearman s) tests, depending on the normality and distribution of the data.	Time 1
Evaluate the physiologic pain measure (Neuropathy Index) on sensitivity to change in pain	Sensitivity to change will be measured through paired t-tests or Wilcoxon signed-rank test, depending on the normality and distribution of the data, to evaluate the statistical significance of the change in scores. We also may use standardized response means, which is a type of effect size, and one of the best methods to estimate responsiveness of measures.	Time 1, repeated 4 weeks to 18 months later (Time 3)
Evaluate safety of physiologic pain assessment	Evaluated by collection and assessment of ADEs (adverse device effects).	Time 1, Time 2, Time 3

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Pamela L Wolters, Ph.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: July 17, 2024
• First Submitted That Met QC Criteria: July 17, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 6, 2026
• Last Verified: June 2, 2026

More Information

Terms related to this study

• Keywords: Biomarker; Pain; Neurofibromatosis Type 1; Clinical outcomes; Sensation; Plexiform Neurofibromas; Objective measurement
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neoplasms; Neuromuscular Diseases; Genetic Diseases, Inborn; 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; Neurofibroma; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurofibromatoses; Pain; Neurofibromatosis 1; Neurofibroma, Plexiform
• Other Study ID Numbers: 10001826; 001826-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review.
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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