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

Neurofibromatosis 1 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02544022
• Other study ID #: 150195
• Secondary ID: 15-C-0195
• Status: Recruiting
• Start date: November 13, 2015
• Est. completion date: December 30, 2025

Study information

• Verified date: June 3, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Pamela L Wolters, Ph.D.
• Phone: (240) 760-6035
• Email: woltersp[@]mail.nih.gov
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 486
• Est. completion date: December 30, 2025
• Est. primary completion date: June 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 5 Years and older

Eligibility

• 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.

Related Conditions & MeSH terms

• Neurofibroma
• Neurofibroma, Plexiform
• Neurofibromatoses
• Neurofibromatosis 1
• Plexiform Neurofibromas

Locations

Country	Name	City	State
United States	Johns Hopkins University	Baltimore	Maryland
United States	National Institutes of Health Clinical Center	Bethesda	Maryland
United States	University of Chicago	Chicago	Illinois
United States	Cincinnati Children's Hospital and Medical Center Institution	Cincinnati	Ohio
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Realiability	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
Primary	Feasability	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	To provide normative data	To provide normative data on these measures of pain intensity and pain interference in individuals with NF1 and pNFs	8 months
Secondary	Convert the measures into electronic format	Convert the measures (including any changes) into an electronic format.	8 months

External Links

•   NIH Clinical Center Detailed Web Page