Acceptance and Commitment Training for Adolescents and Young Adults With Neurofibromatosis Type 1, Plexiform Neurofibromas, and Chronic Pain

Neurofibromatosis Type 1 Clinical Trial

Official title:

Acceptance and Commitment Training for Adolescents and Young Adults With Neurofibromatosis Type 1, Plexiform Neurofibromas, and Chronic Pain: A Phase III Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02471339
• Other study ID #: 150142
• Secondary ID: 15-C-0142
• Status: Completed
• Phase: Phase 3
• Start date: July 7, 2015
• Est. completion date: December 23, 2020

Study information

• Verified date: May 2022
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background:

• People with neurofibromatosis type I (NF1) and plexiform neurofibroma (PN) tumors often have chronic pain that his hard to control. People usually take medicines for the pain, but they may not work well and might cause side effects. A new strategy called Acceptance and Commitment Training (ACT) may help these people cope with chronic pain. ACT focuses on things like values and living in the moment.

Objective:

• To see if Acceptance and Commitment Training improves pain coping in people with NF1 pain.

Eligibility:

• People age 16-34 who have NF1, 1 or more PN tumors, and pain that interferes with their daily functioning.

Design:

• Participants will be screened with a physical exam, medical history, and questions about their pain.

• Participants will fill out questionnaires about their pain and feelings. Their heart rate will be measured via electrocardiogram (ECG).

• Participants will be divided into 2 groups randomly. One will wait 8 weeks.

• The other will start training right away.

• Participants will have 2 two-hour sessions with an ACT trainer. They will learn techniques for setting goals based on personal values and other ways to cope with pain. They will get a workbook and a compact disc (CD) to take home for practice.

• Participants will do practice exercises at home between sessions. They will get weekly emails with a practice exercise. They will join video chat sessions via home computer with their trainer.

• All participants will return to National Institutes of Health (NIH) after 8 weeks for questionnaires and an ECG. The wait group will then start training. They will return 8 weeks later for questionnaires and an ECG.

• Six months later, they will complete questionnaires from home by computer.

Description:

BACKGROUND:

• Neurofibromatosis type 1 (NF1) is a genetic disorder that affects approximately 1 in 3,500 individuals.

• A number of common clinical manifestations, including plexiform neurofibromas, can cause frequent and significant pain and impact quality of life.

• Often, NF1-related pain is not well-controlled with medication and many of the medications cause significant side effects.

• To our knowledge, only one prior study (by our group) has examined the effectiveness of a psychological intervention for chronic pain in adolescents and young adults (AYA) with NF1.

• Acceptance and Commitment Therapy (ACT), a newer generation of cognitive-behavioral therapy, focuses on encouraging individuals to engage in more adaptive ways of coping with pain.

• The goal of ACT is not to eliminate the person's pain, but to optimize the person's functioning despite their pain

OBJECTIVES:

-To compare pain interference mean score changes from baseline to 8 weeks between the ACT intervention group and the waitlist (WL) group.

ELIGIBILITY:

• Patients 16 - 59 years of age with a confirmed diagnosis of NF1 and greater than or equal to 1 plexiform neurofibroma (PN).

• The patient must obtain a mean score of 2.0 or higher or a score of 3 on three or more items on the Pain Interference Index, and report having pain that interferes with functioning for at least three months.

• The patient must have regular access to a computer or tablet with internet access.

DESIGN:

• This is a psychological intervention study to determine the potential benefit of ACT on pain interference, with patients randomized to the ACT intervention or a wait-list control group.

• Patients will come to the National Institutes of Health (NIH) for a 2-day visit (Time 1). After baseline assessments (questionnaires and ECG) are completed, participants in the ACT group will take part in two 2-hour ACT training sessions. At home, this group will receive weekly emails through week 8, and will participate in further ACT training/educational sessions via video chat at weeks 2, 4, and 6.

• All patients will return to the NIH at week 8 (Time 2) to complete follow-up questionnaires and ECG. At this time, the WL group will cross over and receive the ACT intervention (in-person sessions, weekly emails, and video chat sessions). All patients will complete questionnaires again from home six months following the completion of the intervention.

• To detect a change of .68 standard deviation on the primary outcome measure between the two groups at .80 power, 41 patients per group are needed.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: December 23, 2020
• Est. primary completion date: December 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 59 Years

Eligibility

• INCLUSION CRITERIA FOR PARTICIPANT

1. Patients must be between 16 and 59 years of age at the time of the baseline assessment. Because the research on the effectiveness of Acceptance and Commitment Therapy (ACT) with younger children is still emerging, children 15 and younger will be excluded from the present study.

2. Diagnosis of Neurofibromatosis Type 1 (NF1) through germline mutation OR clinical diagnosis; for the clinical diagnosis of NF1 all study subjects must have two or more diagnostic criteria for NF1 listed below (National Institutes of Health (NIH) Consensus Conference):

• Six or more cafe-au-lait spots (greater than or equal to 0.5 cm in prepubertal subjects or greater than or equal to 1.5 cm in postpubertal subjects)

• Greater than or equal to 2 neurofibromas or 1 plexiform neurofibroma

• Freckling in the axilla or groin

• Optic glioma

• Two or more Lisch nodules

• A distinctive bony lesion (dysplasia of the sphenoid bone or dysplasia or thinning of long bone cortex)

• A first-degree relative with NF1

3. Participants must have documentation of a plexiform neurofibromas (PN), based on either clinical exam or imaging.

4. Patient must self-report having chronic pain for at least the past 3 months that has interfered with their daily functioning, as assessed by the Pain Interference Index (must get a mean score of 2.0 or higher, or score a 3 on three or more individual items).

5. Patients must have regular access to a computer or tablet with internet access.

6. Ability of subject or Legally Authorized Representative (LAR) to understand and the willingness to sign a written informed consent document.

7. No anticipated major changes in their pain treatment regimen (i.e., new class of pain medication starting or change in the class of pain medication) or enrollment on a new treatment study presumed to impact pain in the near future.

8. Subjects must be able to read and comprehend the English language, since the highly trained ACT therapists are not fluent enough to conduct the trainings in Spanish or other languages.

EXCLUSION CRITERIA FOR PARTICIPANT

1. In the opinion of the Principal Investigator (PI) or an Associate Investigator (AI), the subject has significant cognitive or emotional difficulties that would prevent them from being able to understand and/or participate fully in the intervention or the measures.

2. Subjects who are participating in any other treatment studies, either medical or behavioral, specifically for pain management.

3. Subjects who began a medical intervention for treatment of their disease that has a possible impact on pain (including Mitogen-activated Protein/Extracellular Signal-regulated Kinase Kinase (MEK) trials) will not be eligible until after one year on the medical treatment; at that time, eligibility will be discussed with the PI of the medical study to assess the stability of the patient s pain and whether further pain-related changes due to the medical treatment are likely.

4. Inability to travel to the NIH, for example, due to physical limitations, for the in-person evaluation(s).

No groups in regards to gender, race, or ethnicity are being excluded from participation in the trial.

Related Conditions & MeSH terms

• Chronic Pain
• Neurofibroma
• Neurofibroma, Plexiform
• Neurofibromatoses
• Neurofibromatosis 1
• Neurofibromatosis Type 1
• Plexiform Neurofibromas

Intervention

Behavioral:
• Acceptance and Commitment Therapy (ACT)
Acceptance and Commitment Therapy (ACT), a newer generation of cognitive-behavioral therapy, focuses on encouraging individuals to engage in more adaptive ways of coping with pain.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

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
Other	Number of Participants With Serious and/or Non-serious Adverse Events	Here is the number of participants with serious and non-serious adverse events. A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	Baseline, and Week 8, 16, 32, and 40.
Primary	Mean Pain Interference Mean Score Change From Baseline to 8 Weeks Between the Acceptance and Commitment Therapy Intervention Group and the Waitlist Group	Pain interference mean score changes were compared between the two groups from baseline to 8 weeks using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference Scale.T-scores typically can range from 0 to 100, with "average" scores ranging from 41-59. No subscales are included in this measure. Higher scores indicate more pain interference (worse).; A two-way repeated-measures analysis of covariance (ANCOVA) was used to examine changes between groups from baseline to the 8-week follow-up.	Baseline and 8 weeks
Secondary	Change in Quality of Life (QOL) for Physical Functioning	Baseline to post-treatment changes in disease-related quality of life was assessed various aspects of quality of life using a subscale from the Pediatric Quality of Life Inventory (PedsQL) Neurofibromatosis Type 1 (NF) Module adult questionnaire which uses a 0-4 Likert scale (0= never, 4 = almost always). Physical Functioning (7 items; possible range 0-28) subscale was administered. Higher scores are worse. Mean scores are linearly transformed to a 0-100 scale, and then were compared to means and standard deviations of a normative group of patients with Neurofibromatosis Type 1.	Baseline and 8 weeks
Secondary	Mean Pain Acceptance Pre- and Post-treatment	Measure of Pain Acceptance pre- and post-treatment was assessed by the Chronic Pain Acceptance Questionnaire (CPAQ) to determine if participants can accept his or her pain. Participants answer 20 questions on a 0 (never true) to 6 (always true) rating scale, with higher scores indicating higher levels of acceptance. Scores are obtained on two subscales (Activities Engagement and Pain Willingness) and an Acceptance Total scale. Only the total score was analyzed for this study. Scores can range from 0 to 120, with higher scores indicating more acceptance (better).	Baseline and 8 weeks
Secondary	Change in Disease-related Pain Severity and Overall Tumor Pain	Pre and post changes in disease-related pain severity and overall tumor pain was assessed using the Numeric Rating Scale - 11 (NRS-11). Two questions rate pain severity on a scale of 0 (no pain) to 10 (worst pain imaginable). For both questions, higher scores = more pain. The two questions are examined separately, there is no total score across items.	Baseline and 8 weeks
Secondary	Change in Quality of Life (QOL) for Daily Activities	Baseline to post-treatment changes in disease-related quality of life, including Daily Activities was assessed using a subscale from the Pediatric Quality of Life Inventory (PedsQL) Neurofibromatosis Type 1 (NF) Module adult questionnaire which uses a 0-4 Likert scale (0= never, 4 = almost always). Daily Activities (12 items; possible range 0-48) subscale was administered. Higher scores are worse. Mean scores are linearly transformed to a 0-100 scale, and then were compared to means and standard deviations of a normative group of patients with Neurofibromatosis Type 1.	Baseline and 8 weeks
Secondary	Change in Disease-related Depression	Pre and post changes in disease-related depression was assessed using the 20-item Center for Epidemiological Studies - Depression scale (CES-D). Participants rate symptoms they have experienced in the past week and items are scored on a 0 (rare or none of the time) to 3 (most of all of the time) scale. Individual responses yield scores on four subscales: depressive affect, positive affect, somatic activity, and interpersonal. A total depression score is obtained that can range from 0 to 60, with higher scores representing worse depressive symptoms.	Baseline and 8 weeks
Secondary	Change in Pain-related Anxiety	Pre and post changes in disease-related pain-related anxiety was assessed by the Pain Anxiety Assessment Scale - 20 (PASS-20). Items are answered on a 6-point Likert scale with anchors of "never" and "always" which provides a total score and scores on four subscales for Cognitive Anxiety, Pain-related Fear, Escape and Avoidance, and Physiological Anxiety. We only examined the total score on this measure, which can range from 0 to 100; higher scores indicate more anxiety.	Baseline and 8 weeks
Secondary	Change in Heart Rate Variability (HRV)	Pre and post changes in disease-related HRV was assessed using an electrocardiogram (EKG). An EKG records electrical signals from your heart. The EKG reading will occur for 5 minutes while the patient is lying down and measurements, including the standard deviation of the average NN (normal-to-normal) interval (SDANN) and the square root of the mean squared differences of successive NN intervals is recorded, resulting in a metric of parasympathetically mediated (high frequency) HRV in milliseconds.	Baseline and 8 weeks
Secondary	Pain Interference Patient-Reported Outcomes Measurement Information System (PROMIS) II	The psychometric properties of the pain interference measure PROMIS was administered to assess pain interference. And adult (18-59 years) and pediatric (16 -17 years) questionnaire was administered to assess how pain interferes with sleep, mood, and leisure activities for instance. Items were formatted on 0-4 Likert scales (0 = Never, 4 = Almost Always) and transformed to T-scores. The PROMIS Pain Interference Scale takes less than 5 minutes to complete and is required of all participants. T-scores typically range from the 20s to 80s with a mean of 50 and standard deviation of 10 ("average" scores range from 40 - 60). No subscales are included in this measure. Higher scores indicate more pain interference (worse). The pediatric and adult versions are made to be parallel so we analyzed all participants together across ages. A two-way repeated-measures analysis of variance (ANOVA) was used to examine changes between groups from baseline to the 8-week follow-up.	Baseline and 8 weeks
Secondary	Measure of Pain Inflexibility Pre- and Post-treatment	Pre- and post-treatment pain interference was assessed using the 12-item Psychological Inflexibility in Pain Scale (PIPS). Participants rate their avoidance of activities because of their pain on a Likert scale of 1 (never true) to 7 (always true). Eight of the items are summed to yield a score on the Avoidance subscale, and four of the items are summed for the Fusion subscale. A total score also is obtained by summing all 12 items. We analyzed only the total score in this study, which can range from 12-84, with higher scores indicating more inflexibility (worse).	Baseline and 8 weeks

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