Background: People with neurofibromatosis 1 (NF1) who have plexiform neurofibromas (PNs) 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 PNs. Eligibility: People ages 5 and older with NF1 and a PN 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 PNs affect their life. They will have group discussions of up to 8 people of a similar age with NF1 and PNs, 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 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.



Eligible Ages
Between 5 Years and 99 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  • Documented NF1 either by NIH clinical criteria or molecularly-proven mutation in the NF1 gene AND Greater than or equal to 1 plexiform neurofibroma in any location that is either symptomatic or asymptomatic, and is defined by the following:
  • 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;
  • measures greater than or equal to 3cm on longest diameter by visual exam, palpation or 2D MR imaging OR greater than or equal to 3mL by volumetric MR imaging.
  • Age greater than or equal to 5 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 and speak the English language.
  • For phase 1 focus groups only, patients need to report experiencing PN 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 PN related pain recently with a minimum pain level of 1 on the current NRS-11.
  • For phase 2, participants in the group evaluating sensitivity to change will need to be starting a new pain medication regimen or increasing the dose of their existing pain medication, or starting a drug to reduce PN size.
  • Parent or Guardian Inclusion Criteria
  • Parent or Guardian of participating subject
  • Participants must be able to understand 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.
  • For phase 2, patients participating in the test-retest subgroup cannot be enrolled on a clinical trial or cannot have started a new pain treatment regimen at their appointment (e.g., medication, therapy, physical therapy, etc.)

Study Design

Study Type
Observational Model
Time Perspective

Arm Groups

ArmDescriptionAssigned Intervention
1/Phase 1 Focus Group Patients with NF1 who have PNs and report experiencing PN related pain and parents ofthese patients. (completed)
2/Phase 1 Patients Patients with NF1 who have PNs
3/Phase 1 Parent Parents of patients in cohort 2
4/Phase 2 Patients Patients with NF1 who have PNs
5/Phase 2 Parents Parents of patients enrolled in cohort 4

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia

More Details

National Cancer Institute (NCI)

Study Contact

Pamela L Wolters, Ph.D.
(240) 760-6035

Detailed Description


- Neurofibromatosis 1 (NF1) is a genetic disease with multiple clinical manifestations, including plexiform neurofibromas (PN) 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 PN shrinkage.

- A critical step toward approval of drugs to treat PNs 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 atrials, especially for assessing changes in symptoms, such as pain.

- Currently, no valid PRO measures exist that are specific to the NF1 population to assess PN pain, its functional impact on an individual s life, or overall physical functioning, which may be affected by PNs.


- Phase 1: Qualitative Evaluation

---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.

- Phase 2: Evaluation of Psychometric Properties and Collection of Normative Data

- 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.


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.


This protocol will be a limited site, multi-institutional research study to maximize our ability to assess a large, diverse sample of individuals with NF1. NCI is the lead institution and the three participating sites are Children s National Medical Center, University of Chicago, and Cincinnati Children s Hospital.

This study will consist of 2 phases:

- Phase 1: Qualitative Evaluation

--The first phase involves evaluation of current modifications and the need for any additional modification of the NRS-11 and the PII and evaluating the most appropriate items from the PROMIS-PF item bank to use in the PROMIS-PF short form by conducting focus groups and interviews with patients diagnosed with NF1 and PNs and parents of children. We will conduct up to 24 focus groups across various age bands. We will conduct up to four groups of 6-8 subjects for each age band (8-11 years; 12-14 years; 15-19 years [still in high school]; 18- 24 years [graduated from high school]; 25+ years; and parents of children with NF1). In lieu of focus groups with young children (ages 5-7), we will conduct individual cognitive interviews. We will conduct up to 6 interviews for children ages 5, 6, and 7, resulting in up to 18 child cognitive interviews; we will additionally conduct up to 6 cognitive interviews with parents of children 5-7. This qualitative data will be evaluated and any necessary changes based on patient responses, will be made to the NRS-11, PII, and PROMIS-PF. The measures will then be converted into an electronic format that will have the same items and will have the same question and answer format as the paper questionnaires. It will be administered on an electronic tablet. We will then conduct up to 32 cognitive interviews across 3 broad age bands (8-12, 13-19, and 18+) up to 10 cognitive interviews with parents, and up to 20 additional interviews across age bands if deemed necessary following qualitative analysis for a maximum ceiling of 62 patients with a target of 42 cognitive interviews to evaluate the measures. Based on these qualitative results these versions will be updated if necessary to prepare for phase 2.

- Phase 2: Evaluation of Psychometric Properties and Collection of Normative Data

- The second phase will evaluate the final electronic versions of the NRS-11, the PII, and the PROMIS-PF using a cross-sectional design to examine internal consistency, construct validity, sensitivity to change, and to provide normative data on the study measures for the NF1 population. It is our goal to recruit from 14 to 16 patients, with a target of 15 in each of 8 phase 2 age bands for an approximate ceiling of 128 (target = 120) patients, 64 parents of children (target = 60) 8+ and 16 parents of children ages 5-7 (target = 15). All patients and parents will be asked to complete the measures two different times to examine test-retest reliability or sensitivity to change. For the sensitivity to change analysis, a subset of patients will be given the measure before and after starting a new pain medication treatment (including new prescriptions and dose escalations) or starting a new drug to reduce tumor size.


Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.