Medication Adherence in Children, Adolescents and Adults With Neurofibromatosis Type 1(NF1) on Clinical Treatment Trials

Neurofibromatosis 1 Clinical Trial

Official title:

Pilot Study of Medication Adherence in Children, Adolescents, and Adults With Neurofibromatosis Type 1 (NF1) on Clinical Treatment Trials

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03531814
• Other study ID #: 180093
• Secondary ID: 18-C-0093
• Status: Completed
• Phase: N/A
• Start date: October 23, 2018
• Est. completion date: March 20, 2023

Study information

• Verified date: May 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background:

Neurofibromatosis type 1 (NF1) is a genetic disorder. It has a broad variety of effects on the body. Up to half of people with NF1 get plexiform neurofibromas (PNs). These are benign tumors. But they can have serious effects like pain and disfigurement. To treat PNs, a person may have to take medicine every day for a long period of time. Researchers think that it will be important for people to take the medicine regularly for it to work. They want to study how well people with NF1 follow their treatment plan for PNs.

Objective:

To study how often people with neurofibromatosis type 1 take medicine that has been prescribed to them for treating plexiform neurofibromas.

Eligibility:

People ages 3-59 already enrolled in an NF1 clinical trial

Design:

Participants will need access to the internet to do the study activities.

Parents or caregivers will do some study activities for child participants.

Participants will complete 5 questionnaires. They will take about 20 minutes total. The topics will be:

Demographic data

Recent life events

How much pain interferes with daily life

Ability to focus and pay attention to tasks

Emotional distress or depression

Participants will mark down every time they take a dose of the medicine in their clinical trial. They will use a form the researchers give them. The pill bottles they get in their trial will have a chip in the cap that will record when it is opened. Participants will keep a daily diary of their medicine. Their pills will be counted at clinical trial visits.

Participants may have more short questionnaires. They may have interviews by phone or video.

Description:

Background:

• Neurofibromatosis type 1 (NF1) is a genetic disorder that affects approximately 1 in 3,500 individuals and is associated with a broad variety of symptoms and physical findings.

• Plexiform neurofibromas (PN) are histologically benign tumors which occur in 25-50% of patients with NF1 and can lead to significant morbidity.

• Oral therapeutic options for the treatment of plexiform neurofibromas are being actively developed, however early clinical data indicate that prolonged treatment over the course of months to years will likely be needed to maintain clinical efficacy

• Long-term medication adherence is an ongoing challenge for patients with many types of chronic illness, and clinical experience makes us strongly suspect patients with NF1 will likely have this issue as well.

• In other diseases, such as human immunodeficiency virus (HIV) and Acute Lymphoblastic Leukemia, decreased medication adherence has been associated with poorer clinical outcomes, and this may be the case for NF1 as well.

• The medication event monitoring systems (MEMS^TM) uses a computerized method of tracking the dates and times of a pill bottle being opened and has been shown to be a more accurate measure of medication adherence than patient diaries or pill counts in other patient populations.

• Assessing medication adherence over time in this unique population will be essential for assessing any impact on medical outcomes, identifying potential behavioral interventions, and targeting patients most at risk for nonadherence moving forward.

Objective:

• To establish the feasibility of using MEMS^TM to monitor medication adherence in the NF1 population

Eligibility:

• Subjects must have a diagnosis of NF1 and be between 3 and 59 years of age

• Participants must be enrolled on a clinical trial for an oral medication in pill (tablet or capsule) form directed at the treatment of plexiform neurofibroma(s)

Design:

• This single-site, longitudinal study will recruit children and adults with NF1 who are currently enrolled in a treatment protocol for a drug targeting PN volume reduction.

• MEMS^TM caps will be used to monitor adherence over time along with patient diaries and pill counts.

• Patients with MEMS^TM cap data indicating <90% adherence at any study visit (typically across 3 - 6 cycles) will be administered a measure assessing barriers to adherence electronically and will be interviewed to evaluate what factors might contribute to decreased medication adherence and what potential interventions they consider useful.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: March 20, 2023
• Est. primary completion date: March 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 59 Years

Eligibility

• INCLUSION CRITERIA:

Inclusion Criteria for Patient

• Patients must be between 3 and 59 years of age at the time of the baseline assessment.

• Patients must be enrolled on a neurofibromatosis Type 1 (NF1) clinical trial for an oral medication directed at the treatment of plexiform neurofibroma(s) (enrollment on this study to occur ideally within 1st cycle) Patients must have regular access to a computer or electronic device (e.g., smartphone, tablet) with internet access.

• Must have a parent or adult primary caregiver willing to participate in the study.

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

• Subjects must be able to read and comprehend the English language.

Inclusion Criteria for Parents or Caregivers

• Must be a parent or primary caregiver of a child (or if applicable adult patient) of diagnosed with NF1 and enrolled on a clinical trial for oral medication.

• Must have a child (or if applicable adult patient) willing to participate in the study

• Must have regular access to a computer or electronic device (e.g., smartphone, tablet) with internet access.

• Must be able to speak and understand English.

• Ability of subject to understand and the willing to sign a written informed consent document.

EXCLUSION CRITERIA:

Exclusion Criteria for Patient

• 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 study or complete the measures. Though these patients might be receiving assistance in taking medication from a caregiver, it is likely that their medication taking routine would be significantly different from the general population of patients with NF1.

• Patients receiving the study drug in liquid form, since the use of medication event monitoring systems (MEMS^TM) caps prohibits liquid dosing.

Exclusion Criteria for Parent or Caregiver

None

Related Conditions & MeSH terms

• Neurofibroma
• Neurofibroma, Plexiform
• Neurofibromatoses
• Neurofibromatosis 1

Intervention

Behavioral:
• Medication Event Monitoring System (MEMS^TM)
A computerized method of tracking the dates and times of a pill bottle being opened.

Other:
• Questionnaires
Adult and pediatric participants completed a series of questionnaires to assess medication adherence, demographics, life events, and barriers to adherence.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	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/or 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 to cycle 18 (end of study), approximately 504 days (1.38 years)
Primary	Proportion of Enrolled Participants for Which we Are Able to Collect Data From the Medication Event Monitoring Systems (MEMS^TM) System for Two or More Cycles of Treatment (Target = 75%)	The proportion of enrolled participants are reported for individuals who had two full cycles of data recorded by the medication event monitoring systems (MEMS^TM) system. To monitor medication adherence the medication event monitoring system (MEMSTM) used to track the dates and times a pill bottle was opened. At least 2 cycles of medication adherence are considered a success.	Two cycles, approximately 56 days
Primary	Median Number of Cycles Monitored for Participants From the Medication Event Monitoring System (MEMS^TM)	To monitor medication adherence the medication event monitoring system (MEMSTM) was used to track the dates and times a pill bottle was opened. We calculated the median number of cycles monitored for all patients.	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days
Secondary	Average Percent Medication Adherence Over Time Based on the Medication Event Monitoring Systems (MEMS^TM) Pill Cap Data	To monitor medication adherence the medication event monitoring system (MEMS^TM) was used to track the dates and times a pill bottle was opened. The number of times the bottle was opened was divided by the total number of times the bottle should be opened according to provider instructions. The mean of these numbers was computed across groups of cycles 1-4, 5-8, 9-12 and 13-18. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. Higher number is better adherence.	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days
Secondary	ANOVA (Analysis of Variance) Comparing Average Adherence Measured by Medication Event Monitoring Systems (MEMS^TM), Medication Diary, and Pill Count	A repeated-measures ANOVA was used to compare three adherence assessment methods over time. The medication event monitoring system (MEMS^TM) was used to track the dates and times a pill bottle was opened. The number of times the bottle was opened was divided by the total number of times the bottle should be opened according to provider instructions. Pill count was used to assess how many pills were returned at each restaging visit compared to the number that should be returned if all medication was taken as prescribed. The daily diary was completed by participants, documenting date and timing of doses. The mean of these numbers was computed across groups of cycles (1 cycle = 28 days) 1-4, 5-8, 9-12 and 13-18 for the MEMS^TM, Pill Count, and Daily Diary.	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), an range of approximately 112 days to 504 days
Secondary	Spearman Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Age	The outcome measures correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS^TM cap and age, Spearman correlation was used. For this analysis, MEMS^TM was defined as the average mean adherence for cycles 1-4, cycles 5-8, cycles 9-12, and cycles 13-18. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average.	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days
Secondary	Spearman Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap for Years of Education	The outcome measures correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS^TM cap for years of education, Spearman correlation was used. For this analysis, MEMS^TM was defined as the average mean adherence for cycles 1-4. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. Number of years of education was collected through participant self-report and was a continuous variable.	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days
Secondary	Spearman's Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Quality of Life (QOL) Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference T-scores	Outcome measures correlations between 2 variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS^TM cap & PROMIS Pain Interference T- Scores (Same for all PROMIS measures) Spearman correlation was used. For this analysis, MEMS^TM was defined as the average mean adherence for cycles 1-4. A dose was considered adherent if it was taken within an 11-13hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle & dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. PROMIS Pain Interference raw scores transformed to T-scores for analysis (mean:50,standard deviation: 10, higher scores is more pain interference, T of 55 is cutoff-mild pain interference).	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days
Secondary	Spearman's Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Quality of Life (QOL) Patient-Reported Outcomes Measurement Information System (PROMIS) Depression T-scores	The outcome measures correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS^TM cap and PROMIS Depression Scores, Spearman correlation was used. For this analysis, MEMS^TM was defined as the average mean adherence for cycles 1-4. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. PROMIS Depression raw scores were transformed to T-scores for analysis (mean: 50, standard deviation: 10, higher scores is more depression symptoms, T of 55 is the cut off for mild depressive symptoms).	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days
Secondary	Spearman's Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Quality of Life (QOL) Patient-Reported Outcomes Measurement Information System (PROMIS) Cognitive Interference T-scores	The outcome measures correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. To assess the relationship between the adherence method MEMS^TM cap and PROMIS Cognitive Interference Scores, Spearman correlation was used. For this analysis, MEMS^TM was defined as the average mean adherence for cycles 1-4. A dose was considered adherent if it was taken within an 11-to-13-hour interval from the prior correct dose. The mean was computed by summing medication adherence across the cycle and dividing it by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data to compute the average. PROMIS Cognitive Interference raw scores were transformed to T-scores for analysis (mean: 50, standard deviation: 10, higher scores is more cognitive interference, T of 60 represents mild interference).	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days
Secondary	Barriers to Adherence Questionnaire	Participants completed a barriers questionnaire to assess barriers most frequently endorsed on the questionnaire. The questionnaire focused on any medication adherence issues during the trial (e.g., missed doses). Participants were given 16 possible reasons that they may have missed a dose and were asked to check all items that caused them to miss a dose of medication. Participants were also able to provide additional reasons for missing medication that were not on the form.	Baseline and follow-up (between cycles 8 and 12; or after cycle 18/when taken off of study (range of 224-504 days)
Secondary	Spearman's Correlation of the Relationship Between Medication Event Monitoring Systems (MEMS^TM) Cap and Barriers to Adherence Questionnaire	The outcome measures Spearman correlations between two variables and the resulting correlation coefficient describes the strength of the relationship between the variables. MEMS^TM was defined as the average mean adherence, an adherent dose was taken 11-13 hours from the prior correct dose. The mean was computed by dividing medication adherence across the cycle by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data. Barriers to adherence was calculated by summing the number of barriers for each participant at follow-up. Participants were given 16 possible reasons that they may have missed a dose and were asked to check all items that apply to them.	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days
Secondary	Medication Event Monitoring Systems (MEMS^TM) Cap and Stressful Life Events: Number of Stressful Life Events Endorsed in the Life Events Checklist	To assess the relationship between the adherence method MEMS^TM cap and stressful life events (i.e., the number of stressful life events endorsed in the Life Events Checklist), Spearman correlation was used. Participants complete a 22-item questionnaire to report stressful events that impact medication adherence. MEMS^TM was defined as the average mean adherence, an adherent dose was taken 11-13 hours from the prior correct dose. The mean was computed by dividing medication adherence across the cycle by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data.	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days
Secondary	Medication Event Monitoring Systems (MEMS^TM) Cap and Rating of Overall Stress	To assess the relationship between the adherence method MEMS^TM cap and rating of overall stress, Spearman correlation was used. Participants complete a 1-item question asking them to rate their stress from 0 - 10, with higher numbers being more stressed. MEMS^TM was defined as the average mean adherence, an adherent dose was taken 11-13 hours from the prior correct dose. The mean was computed by dividing medication adherence across the cycle by the number of days within the cycle. Then, the average mean was calculated by using Statistical Package for the Social Sciences (SPSS) MEAN function, which uses all non-missing data.	Cycles 1-4, 5-8, 9-12 and 13-18 (1 cycle = 28 days), a range of approximately 112 days to 504 days

External Links

•   NIH Clinical Center Detailed Web Page