Development and Validation of Patient Reported Outcome (PRO) Measures for Individuals With Neurofibromatosis 1 (NF1) and Plexiform Neurofibromas (pNFs)

February 21, 2024 updated by: National Cancer Institute (NCI)

Background:

People with neurofibromatosis 1 (NF1) who have plexiform neurofibromas (pNFs) can have pain that affects their daily lives. This study aims to improve questionnaires that measure their pain, daily living, and physical functioning.

Objectives:

To examine and improve questionnaires about daily living for people with NF1 and pNFs.

Eligibility:

People ages 5 and older with NF1 and a pNF

Design:

Participants will be screened with medical history.

This study will have 2 phases.

Phase 1 participants will talk about existing pain assessment questionnaires and how pNFs affect their life. They will have group discussions of up to 8 people of a similar age with NF1 and pNFs, or the parents of children with it. These will last about 90 minutes. Children ages 5 to 7 and their parents will have one-on-one meetings instead. These will last about 45 minutes. Discussions will be audiotaped. After the questionnaires have been changed, individual interviews will discuss the new wording, instructions, questions, and electronic format of the new forms.

Phase 2 is now complete.

Phase 1 participants may be invited to Phase 2.

Phase 2 participants will complete the new questionnaires. These may be pen-and-paper or electronic. The questionnaires will take about 30 minutes for adults and teens. Children will work one-on-one with a staff member and may need up to 45 minutes. A small group of participants will be complete the forms twice-in clinic and 1 month later at home. Also, a small group who start a new pain treatment or have a dose increase in their treatment will complete the forms twice-before the treatment change and 1 month later.

Study Overview

Status

Recruiting

Detailed Description

Background:

  • Neurofibromatosis 1 (NF1) is a genetic disease with multiple clinical manifestations, including plexiform neurofibromas (pNFs) that can cause pain and may significantly impact daily functioning and quality of life (QOL).
  • Patient-reported outcomes (PROs) are useful in trials for conditions that are disabling and chronic like NF1, where symptom reduction and improved functioning and QOL currently are important treatment outcomes, which may occur with pNF shrinkage.
  • A critical step toward approval of drugs to treat pNFs is to evaluate clinical benefit in conjunction with a reduction in tumor volume as assessed by imaging endpoints.
  • The FDA requests the use of PROs in NF1 clinical trials, especially for assessing changes in symptoms, such as pain.
  • Currently, no valid PRO measures exist that are specific to the NF1 population to assess pNF pain or its functional impact on an individual s life.

Objectives:

  • Phase 1: Qualitative Evaluation - COMPLETE

    --To evaluate current modifications and the need for any additional modifications to existing measures of pain intensity (Numeric Rating Scale; NRS-11) and pain interference (Pain Interference Index; PII) and select the most appropriate items to measure physical functioning (PROMIS Physical Functioning; PROMIS-PF) in NF1 based on qualitative feedback from patients with NF1, pNFs and pain to use as endpoints in clinical trials for individuals with NF1 and pNFs.

  • Phase 2: Evaluation of Psychometric Properties and Collection of Normative Data
  • To evaluate final versions of the NRS-11 (now called the PAin INtensity Scale for pNF [PAINS-pNF]) and PII (now called the Pain Interference Index for pNF [PIIpNF]) measures on reliability, validity, and feasibility in individuals with NF1 and pNFs.

Eligibility:

  • Patients with documented NF1 either by NIH clinical criteria or molecularly-proven mutation in the NF1 gene will be included in the study. Patients must have at least 1 plexiform neurofibroma (pNF) that is at least 3cm on longest diameter by physical exam (i.e. visual exam, palpation) or 2D MR imaging OR >=3mL by volumetric MR imaging. Patients must be at least 8 years of age and able to understand, read, and speak English.
  • Patients will be ineligible if they were enrolled on a MEK inhibitor trial in the past 12 months or began a new pain treatment regimen (e.g., medication, psychosocial therapy, physical therapy, etc.) within the past three months at the time of recruitment.
  • Primary caregivers (i.e. parent, guardian, grandparent) of participants younger than 18 years old are also eligible to participate in order to provide parent report information to further validate the PII-pNF questionnaire for parents.

Design:

  • This protocol will be a multi-institutional research study to maximize our ability to assess a large, diverse sample of individuals with NF1.
  • This study will consist of 2 phases. During the first phase, we conducted the qualitative portion of the study with individuals with NF1, ages >=5 years, most with pNF-related pain, using both focus groups and individual interviews. During Phase 2, we will evaluate the final electronic versions of the PAINS-pNF and the PII-pNF using a microlongitudinal design to examine internal consistency, construct validity, and test-retest reliability, and to provide normative data on the study measures for the NF1 population.
  • Our goal for phase 2 is to recruit between 14 to 16 patients, with a target of 15 in each of the eight phase 2 age bands for an approximate ceiling of 128 patients >=8 years old (target = 120) and 48 parents of children 8-17 years old (target = 45). All patients and parents will be asked to complete the measures two weeks in a row to examine test-retest reliability.

Study Type

Observational

Enrollment (Estimated)

486

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Completed
        • Children's National Medical Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Active, not recruiting
        • University of Chicago
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Completed
        • Johns Hopkins University
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Contact:
          • National Cancer Institute Referral Office
          • Phone Number: 888-624-1937
    • Ohio
      • Cincinnati, Ohio, United States, 45229-3039
        • Completed
        • Cincinnati Children's Hospital and Medical Center Institution
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Completed
        • Children's Hospital of Philadelphia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Patients with documented NF1 either by NIH clinical criteria or molecularly-proven mutation in the NF1 gene will be included in the study. Patients must have at least 1 plexiform neurofibroma (PN) that is at least >3cm on physical exam or >3mL on volumetric MRI. Patients must be at least 5 years of age and able to understand and speak English.

Description

  • SUBJECT INCLUSION CRITERIA:
  • Documented NF1 either by NIH clinical criteria or molecularly-proven mutation in the

NF1 gene, PER the Neurofibromatosis Diagnostic Criteria AND >=1 plexiform neurofibroma in any location that is either symptomatic or asymptomatic, and is defined by the following:

  1. a neurofibroma that has grown along the length of a nerve and may involve multiple fascicles and branches OR a spinal neurofibroma that involves two or more levels with connection between the levels or extending laterally along the nerve OR a skin thickness neurofibroma;
  2. measures >=3cm on longest diameter by visual exam, palpation or 2D MR imaging OR >=3mL by volumetric MR imaging.

    • For phase 1, Age >=5 years. (complete)
    • For phase 2, Age >= 8 years
    • Ability of subject or parent or guardian to understand and the willingness to sign a written informed consent document.
    • Participants must be able to understand, read, and speak the English language.
    • For phase 1 focus groups only, patients need to report experiencing pNF related pain recently with a minimum pain level of 3 on the current NRS-11 or report taking prescription medication that reduces pain and experiencing pNF related pain recently with a minimum pain level of 1 on the current NRS-11. (complete)
    • For phase 2, patients need to report recently experiencing at least a minimal amount of pNF-related pain. Specifically, they will be asked if they recently experienced any pain in a target tumor area and will have to respond yes to be eligible..

PRIMARY CAREGIVER INCLUSION CRITERIA:

  • Primary caregiver (i.e. parent,guardian, grandparent) who is >= 18 years old of participating subject <= 17 years old
  • Participants must be able to understand, read, and speak the English language

EXCLUSION CRITERIA:

  • Patients with severe cognitive or behavior impairments who, in the judgment of the investigators, would not be able to cooperate with the study procedures will be excluded.
  • Patients cannot be newly enrolled on a clinical trial to treat their pNF or cannot have started a new pain treatment regimen (e.g., medication, psychosocial therapy, physical therapy, etc.) at the time of enrollment. Specifically, patients will be ineligible if they were enrolled on a MEK inhibitor trial in the past 12 months or began a new pain

medication or treatment within the past 3 months prior to enrollment on this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
1/Phase 1 Focus Group
Patients with NF1 who have PNs and report experiencing pNF related pain and parents of these patients. (completed)
2/Phase 1 Patients
Patients with NF1 who have pNFs(completed)
3/Phase 1 Parent
Parents of patients in cohort 2 (completed)
4/Phase 2 Patients
Patients with NF1 who have pNFs and recent pNF-related pain
5/Phase 2 Parents
Parents of patients (ages 8-17 years) enrolled in cohort 4

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Realiability
Time Frame: 8 months
To evaluate final versions of the NRS-11, PII, and PROMIS-PF measures on reliability, validity, sensitivity to change, and feasibility in individuals with NF1 and PNs.
8 months
Feasability
Time Frame: 8 months
To evaluate current modifications and the need for any additional modifications to existing measures of pain intensity (Numeric Rating Scale; NRS-11) and pain interference (Pain Interference Index; PII) and select the most appropriate items to measure physical functioning (PROMIS Physical Functioning; PROMIS-PF) in NF1 based on qualitative feedback from patients with NF1, PNs and pain to use as endpoints in clinical trials for individuals with NF1 and PNs. (completed)
8 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To provide normative data
Time Frame: 8 months
To provide normative data on these measures of pain intensity and pain interference in individuals with NF1 and pNFs
8 months
Convert the measures into electronic format
Time Frame: 8 months
Convert the measures (including any changes) into an electronic format.
8 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 13, 2015

Primary Completion (Estimated)

June 30, 2025

Study Completion (Estimated)

December 30, 2025

Study Registration Dates

First Submitted

September 5, 2015

First Submitted That Met QC Criteria

September 5, 2015

First Posted (Estimated)

September 9, 2015

Study Record Updates

Last Update Posted (Estimated)

February 22, 2024

Last Update Submitted That Met QC Criteria

February 21, 2024

Last Verified

February 20, 2024

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

.All IPD recorded in the medical record will be shared with intramural investigators upon request.

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Neurofibromatosis 1

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