Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT04059146 |
Other study ID # |
201904722 |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
September 18, 2019 |
Est. completion date |
March 10, 2021 |
Study information
Verified date |
February 2024 |
Source |
University of Iowa |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This is a randomized double-blind, placebo-controlled trial with individuals who have chronic
Achilles tendinopathy (AT). This study investigates the effects of education on outcomes
(specified in hypotheses below) related to participation in an exercise program. Participants
will be randomized to one of two educational programs. All participants will receive the same
exercise intervention. This study will consent and randomize 66 participants, who will
complete 2 in-person evaluation sessions (baseline, 8-week follow-up), 8 treatment sessions
with a physical therapist (between baseline and 8-week follow-up), and 1 online evaluation
sessions (12-week follow-up).
We hypothesize that 1) a biopsychosocial approach to education will decrease pain (NPRS) and
disability (PROMIS physical function) more than the standard of care for patients with AT, 2)
exercise will improve all three pain mechanisms examined in this RCT (increased PPT,
decreased kinesiophobia, increased number of heel raises).
Description:
This feasibility randomized controlled trial was designed to address the following aims:
Specific Aim 1 examines if education on central pain mechanisms (i.e. biopsychosocial
approach) compared to education on peripheral pain mechanisms (i.e. standard of care
utilizing a biomedical approach) is more effective at reducing pain and disability in a pilot
RCT exercise program for Achilles tendinopathy. We hypothesize that a biopsychosocial
approach to education will decrease pain (NPRS) and disability (PROMIS physical function)
more than the standard of care for patients with AT.
Specific Aim 2 determines which central pain mechanisms (nociplastic pain, pain psychology,
motor dysfunction) are improved by an exercise program, regardless of education group. We
hypothesize that exercise will improve all three central pain mechanisms (increased PPT,
decreased kinesiophobia, increased number of heel raises).
A total of 66 adults with chronic Achilles tendinopathy (AT) will be enrolled (consented and
randomized) in this single-site pilot randomized controlled trial (RCT). All data will be
collected at a single site within an academic medical center. A pilot RCT comparing
effectiveness of exercise with pain education to standard of care, i.e. exercise with
biomedical education. Participants will be randomized to treatment group using a permuted
block randomization scheme stratified by sex and AT type (insertional and midportion).
Participants will complete up to 7 treatment sessions over an 8-week period. With an
anticipated 10% dropout rate, we plan to analyze data on 30 adults with chronic AT per group.
Participants will complete 2 evaluation sessions at baseline and 8-week follow-up. Evaluation
sessions will involve the following 4 types of testing.
1. Clinical exam (including ultrasound imaging)
2. Questionnaires (demographics, symptom description, and psychological) Private,
identifiable information will be collected via questionnaires administered online and
in-person. All data will be entered into a University of Iowa REDCap database, which is
maintained by University of Iowa ITS staff.
2) Movement analysis and verbal pain rating Participants' motion and force will be captured
as they walk, perform heel raises, hop, and do calf stretches within a 3-dimensional motion
analysis with force plates flush with the floor. To monitor pain level throughout
participation, we will have participants verbally rate their pain with each task.
3) Sensory testing (Pain pressure threshold at the hamstring and Achilles bilaterally;
Conditioned pain modulation at the Achilles)
In addition, participants will complete questionnaires at 12-weeks. Participants will attend
7 treatment sessions over approximately 8 weeks. Over this time period participants will
complete the following procedures
1. Questionnaires (exercise adherence, educational quizzes, symptom description) This
private, identifiable information will be collected via questionnaires administered
online and in-person. All data will be entered into a University of Iowa REDCap
database, which is maintained by University of Iowa ITS staff.
2. Exercise participation Participants will be given exercises to do at home in between
treatment sessions. Participants will receive instruction from a physical therapist
prior to doing the exercise at home.
3. Education Participants will be given homework and online quizzes to do at home in
between treatment sessions. The physical therapist will review the educational material
with the participant at each visit.
In addition, a research team member will access the medical records of participants with
Achilles tendinopathy to gain information about the participant's medical history and imaging
related to Achilles tendinopathy.
The sample size was based on a power analysis for the primary outcome measures of Specific
Aims 1 and 2.
Specific Aim 1: This analysis will compare the between group (biopsychosocial vs biomedical
approach to education) changes in pain and disability scores from baseline to 8 weeks and to
12-week follow-up for participants with AT participating in an exercise program. Based on
findings from Moseley et al. for an RCT comparing a 4-week exercise program with education on
central pain mechanisms to standard of care in 49 patients with chronic low back pain, we
anticipate between group differences with Cohen's d greater than or equal to 0.36 for pain
(between group difference across 2 time points=0.75, SD of 1.05 on the NPRS, effect size of
f=0.36) and disability (between group difference across 2 time points=1.95, SD of 2.33 on low
back pain-specific measure, effect size of f=0.42). Under these assumptions, a sample size of
30 patients per group would be needed to reach 80% power for the time averaged difference
between two group means in a repeated measures design with alpha equal to 0.025 (Bonferroni
correction of 0.05/2 for 2 outcomes in Aim 1) to detect a between group effect size of 0.36.
Specific Aim 2: This analysis will compare the within group changes (baseline to 8-weeks and
to 12 weeks) in central pain mechanisms (nociplastic pain, psychosocial factors, motor
dysfunction) with an exercise intervention for participants with AT, regardless of
educational group. The power analysis for this aim is based on data from 3 studies that have
had a moderate to large (Cohen's d greater than or equal to 0.51) treatment effects on
central pain mechanisms. A study led by Dr. Sluka previously found that massage improved PPTs
2 days after an intense exercise protocol with a large effect size (27.6%, SD=14.7%, effect
size= 1.88). Cai et al. found that a 4-week cognitive behavioral therapy program reduced fear
of movement by 8.1 points with a SD of 5.44 (effect size= 1.5). Based on our preliminary data
from the K99 phase, there was a mean improvement of 3.4 repetitions (SD of change= 6.7) in
heel rise performance after an anesthetic injection for the AT group (effect size=0.51). We
used the smallest and population-specific anticipated effect size of 0.51 to calculate the
sample size for Aim 2. Type I error rate of alpha equal to 0.017 (Bonferroni correction of
0.05/3 for 3 outcomes in Aim 2) will be used for this aim to adjust for the multiple
comparisons. The sample size of 60 patients calculated for Aim 1 would allow us to detect an
effect size of d greater than or equal to 0.43 with 80% power under these assumptions.
The normality of the continuous data will be tested by the Shapiro-Wilk test and by examining
the quantile-quantile plot. Normally distributed Continuous variables will be presented as
mean plus or minus SD for normally distributed data and median with interquartile ranges for
non-normally distributed data. When the normality assumption is not met, transformation, such
as log, will be used to complete planned parametric analyses. Type I error rate will be
maintained at 0.05 by using Bonferroni adjustment for multiple comparisons. First, potential
differences between group demographics at baseline will be examined univariately using two
independent samples t-tests and chi-square tests, as appropriate. If differences are
observed, these variables will be used as covariates in the multivariable models.
A modified intention-to-treat principle will be followed, which will include outcome data on
all participants based on the group they were randomized and complete evaluation at 8 weeks.
We will also compare patient characteristics of those who remained in the study to those who
dropped out to determine if data at subsequent time points is consistent with missing at
random.
For Aim 1 we will assess the effect of the interventions on the primary outcomes for pain
(NPRS) and disability (PROMIS physical function) from baseline to 8-weeks and to 12-week
follow-up using linear mixed model for repeated measures. Similarly, for Aim 2 a linear mixed
model for repeated measures will assess the effect of the interventions by group on the
primary outcomes for central pain mechanisms (nociplastic pain: PPT, psychosocial factors:
TSK, motor control: heel raises) from baseline to 8 weeks. For Aims 1 and 2, the factors in
the linear mixed model will include group and time effects. In addition, the significance of
the group*time interaction term, where the group*time interaction tests if the change over
time differs between groups, will also be tested. We will also assess for normality,
linearity, homoscedasticity, and independence of residuals for the multiple regression models
(dependent variables: pain and disability). Statistical significance will be defined by alpha
greater than or equal to 0.05.
Analyses for secondary outcome measures of central sensitization, psychological factors,
motor control, pain and disability for Aims 1 and 2 will be performed using the same
statistical tests described above. Secondary analyses on sex will examine potential sex-based
differences in both Aims 1 and 2 to inform sample size estimates for future clinical trials.
The analyses described above for each aim will be expanded to explore the effect of sex as a
fixed factor and examine interactions with group and time. Using the same data analysis
strategy as described for sex, a secondary analysis on AT type (insertional vs. midportion)
will also be assessed for Aims 1 and 2 to inform recruitment strategies for future clinical
trials.