Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03646084 |
| Other study ID # |
CIBERES-FES2018-05 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 10, 2018 |
| Est. completion date |
February 1, 2020 |
Study information
| Verified date |
January 2020 |
| Source |
Consorcio Centro de Investigación Biomédica en Red, M.P. |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Musculoskeletal pain has become in a major problem related to its prevalence, treatment cost,
absenteeism, quality of life impairment, disability and drugs consumption. The difficulty in
musculoskeletal pain control ends in the abuse of drugs by these patients, including opioids.
This drugs consumption has become a health problem in the United States and around the world
related to their increasing abuse mainly between 2002 and 2011 and has had an impact in the
numbers of deaths caused by opioids prescription (reaching 16,651 deaths in United States in
2010). Pain is clearly associated with sleep disturbances (50-80% of these patients suffer
from a sleep problem), and in turn poor sleep quality leads to increased pain sensitivity.
There is evidence showing that improving sleep disturbance co-occurring pain would improve,
and some may reduce the use of opioids in specific patients on long-term opioid therapy. In
spite of this reciprocal relationship between sleep and pain only few programs take into
account the management of sleep disorders as a non-pharmacological measure for pain control.
The hypothesis is: "to address sleep and circadian disorders (SCD) using a Sleep and
Circadian Intervention Program (SCIP) in patients treated with rehabilitation by chronic
musculoskeletal pain (CMP) optimizes the rehabilitation outcomes and reduces opioids
consumption".
Main goal:
The aim of this PILOT study is to evaluate the feasibility of the protocol of the present
study that aims to assess the improvement in rehabilitation outcomes and decrease in opioid
consumption, through the management of sleep disorders.
Methodology Using a randomised (1:1) controlled feasibility study, 50 men and women will be
included to evaluate methodology and identify the potential outcome of the main project.
Subjects older than 18 years included in a rehabilitation program by musculoskeletal lumbar
pain lasting more than three months will be recruited. Basal Visit (BV): After the signature
of informed consent, a medical history, physical exam, evaluation of the pain perception
(EQ5D5L), quality of life evaluation (SF36 and FOSQ), mood and anxiety (HADS y PASS20),
circadian rhythm study and drugs consumption will be evaluated in both groups. Patients will
be randomized to control group (usual rehabilitation program) or intervention group (usual
rehabilitation program + sleep circadian intervention program-SCIP). The patient in the SCIP
program will received the next intervention: 1) Educational and circadian rhythm
intervention: general sleep hygiene recommendation and promotion of daily physical activity.
2) Sleep studies for sleep quality and sleep disorders diagnosis: full polysomnography 3)
Sleep questionnaires for another sleep disorders. Based on the results of the studies,
patients will be treated according to current guidelines for the management of sleep
disorders. 6 month after the SCIP starts patients will be evaluated in the End of Study Visit
(EOS) as in the BV and also in their functional improvement and health resources consumption.
Description:
Hypothesis: to address sleep and circadian disorders (SCD) using a Sleep and Circadian
Intervention Program (SCIP) in patients treated with rehabilitation by chronic
musculoskeletal pain (CMP) optimizes the rehabilitation outcomes and reduces opioids
consumption.
The Main Objective of this PILOT study is to evaluate the feasibility of the protocol of the
present study that aims to assess the improvement in rehabilitation outcomes and decrease in
opioid consumption, through the management of sleep disorders.
Secondary objectives of the PILOT study:
1. To identify the primary outcome to evaluate the hypothesis. Evaluate relevance and
observed change of the main outcome for the main study. It will allow investigators to
evaluate the effect size and variability of the SCIP in the opioids consumption in a
sample of our population to determine if this is the potential outcome for the main
project.
2. To determine the patient inclusion rhythm (recruitment rate) and, if necessary, the
reasons for non-recruitment.
3. To determine the follow-up rate and reasons for loss to follow-up.
4. To test the sleep circadian study's methodology in this type of population.
5. To assess the acceptability, implementation and preliminary efficacy of the SCIP.
6. To evaluate adherence and fidelity to the SCIP through recruitment and retention.
7. To determine the data acquisition rate, amount of missing data and reasons for loss.
8. To evaluate the safety of the program.
9. To characterize the effect observed in the intervention in order to properly calculate
the sample size necessary for the main study.
Methodology:
Type of study: This study aims to be the pilot project of a large-scale international
randomized controlled trial that will include a total of 1.000 patient internationally. In
this pilot study, using a randomised (1:1) feasibility study, 50 patients in a rehabilitation
program referred to treatment for CMP lumbar pain will be recruited. The pilot study will
have a total duration of 18 months (12 months of recruitment + 6 months follow-up) and all
the interventions included in the methodology of the main study will be carried out in the
participating patients. As a feasibility trial, aspects of feasibility will be determined and
estimates of effect size and measured variability will be calculated to inform future planned
study. The data for this study will be collected from standard measures administered in their
basal visit (BV), immediately prior to the initiation of the SCIP, and 6 months after the
initiation of the program (End of study visit-EOS). Randomisation to allocate participants to
either intervention or control group will be performed immediately following the baseline
assessment, and intervention delivery (SCIP) will begin directly after the BV. Participants
will be then reassessed at 6 months after the baseline (EOS) as in the BV and for functional
improvement and health resources consumption. Inclusion criteria: 1) Subjects older than 18
years 2) Inclusion in a rehabilitation program by musculoskeletal lumbar pain lasting more
than three months 3) Patients have no severe reading or learning difficulty 4) Signature of
informed consent. Exclusion criteria: 1) Severe psychopathological co-morbidity (e.g. the
presence of schizophrenia, bipolar disorders…) 2) Co-morbid malignant/terminal diseases (e.g.
HIV/AIDS, cancer) 3) Shift-workers and people who work making transmeridian travels.
All patients will provide written consent for their data to be used in an anonymized form for
research purposes and project will have ethics and research and development committee
approval prior to the start.
Basal Visit: All participants will be asked to provide in the BV the basic demographic
information, medical characteristics (age, gender, job, medication), pain characteristics
(pain cause, time, location and intensity) and a basic physical exam (blood pressure, height,
weight, neck, hip and waist circumference), a drugs test will be performed to assess opioids
consumption and a circadian rhythm study (individual activity rhythms will be measured
noninvasively with Kronowise® [with European Community marking for this indication] in all
patients). To evaluate the effect of the SCIP pain reduction may not be sufficient for a
comprehensive evaluation of the overall benefit of the intervention. The complexity of
chronic pain and its negative impact on diverse aspects of function should be evaluated: 1a.
To evaluate the improvement of pain perception and pain intensity control: pain intensity,
sensory pain ratings and affective pain ratings will be measured before and after the
intervention in both groups. To provide this multidimensional assessment of pain the 5-level
EQ-5D version (EQ-5D-5L) will be completed in basal visit and after intervention.1b. To
evaluate the improvement in quality of life (QoL) measured it will be measured by QoL
questionnaires (SF36 and FOSQ) before and after the intervention and 1c. To measure the
improvement in mood and anxiety patients will answer the Hospital Anxiety and Depression
Scale (HADS) and Pain Anxiety Symptoms (Scale-PASS20).
Groups: The patients will be selected by their rehabilitation doctor who will establish the
indication and dose of the necessary medication to control the pain, according to the
criteria of conventional clinical practice.
Patients will be randomized to:
1 Control group. Rehabilitation according to current clinical practice. 2 SCIP group.
Rehabilitation according to current clinical practice + specific actions in the treatment
group (the next action in this point 2 will be undergo only in the SCIP group): 2a.
Educational and circadian rhythm intervention: 2a. I - General sleep hygiene recommendations.
2a. II - Promotion of daily physical activity: determine sleep circadian patterns during
rehabilitation: Each participant will record his/her sleep periods in a sleep log. In
addition, individual rest/activity, distal skin temperature and light exposure rhythms will
be measured noninvasively with a watch-like device (Kronowise ®) during 7 consecutive days
and nights. Sleep disturbances as sleep onset latency longer than 30 minutes, more than two
waking episodes per night, total sleep time shorter than 6.5 hours or a sleep efficiency
lower than 85% will be take into account and submitted to the specialist if necessary.
Specific circadian habits modification advise or treatment will be given depending in the
results. All this information will be collected and analysed to determine sleep and circadian
hygiene and the circadian rhythms of the above-mentioned variables in the BV and after the
SCIP (EOS).
2b. Describe the sleep disorders related to chronic pain by applying sleep studies to
evaluate sleep quality and to diagnose sleep disturbances during rehabilitation: full
Polysomnography 2c. Describe other sleep disorders by applying specific questionnaires: To
evaluate quality of sleep the Pittsburgh questionnaire will be performed, the Epworth
Sleepiness scale to assess daytime hypersomnolence and to diagnose other sleep disorders such
as insomnia and restless legs syndrome (RLS) the Insomnia Severity Index (ISI) and the RLS
criteria will completed respectively.
2d. Therapeutic intervention related to the results obtained in the mentioned studies (2 a, b
and c): advice/treatment will be recommended to determine the effect of the specific
interventions decided (pharmacological or non-pharmacological) related to SCD detected in 2
a,b and c. Based on the results of the studies, patients will be treated according to current
guidelines for the management of sleep disorders and taking into account the following
recommendations: 1) Interventions that improve rest/activity rhythms: Sleep Hygiene, bright
light therapy and noise control, time of exercise and feeding. 2) To treat and control Sleep
Disorder Breathing (including adaptive servo-ventilation and bi-level positive airway
pressure ventilation for Central Sleep Apnea if needed). 3) To improve anxiety, depression
and insomnia (to apply bright light therapy and refer to a specialist if needed). 4) To treat
Legs Restless Syndrome if needed. 5) To try opioid dose reduction. 6) To trial of non-opioid
therapies (NSAIDs, antiepileptic drugs, physical therapy, antidepressants…) in lieu of
opioids. 7) Avoiding use of benzodiazepines, sedatives, hypnotics. 8) Caution against alcohol
use.
Blood samples extraction will be obtained from all participants at the beginning of
rehabilitation and at the end of follow-up to study to measure serum levels of inflammatory
and oxidative stress biomarkers implicated in pain control.
EOS visit: After 6 months of the initiation of the SCIP the BV measurements will be repeated
and also an evaluation of the functional improvement and consumption of health resources. The
impact of the SCIP will be evaluated in the next aspects: 1a. Improvement of pain perception
and pain intensity control. 1b. Improvement in quality of life (QoL). 1c. Improvement in mood
and anxiety. 1d. Physical functioning improvement: activity registers from Kronowise ® will
be used to assess the physical activity rhythm improvement (specific measures of the affected
musculoskeletal component). 1e. Consumption of health resources (pharmacological and
non-pharmacological): Pharmacological consumption: Patient pharmacologic sleep and pain
agents and dosing will be recorder at basal visit and after the sleep intervention: opioid
analgesics, benzodiazepine receptor agonists, nonbenzodiazepine benzodiazepine receptor
agonists, melatonin receptor agonists, antidepressants, antipsychotics, anticonvulsants,
general analgesic and antihistaminic drugs. Non-pharmacological consumption: days of
rehabilitation treatment, visits to emergency department, hospitalization related to pain or
CP treatment, duration of sick leave (days of work absenteeism). 1f. Improvement of the
circadian system parameters.
Ethics and Safety: There are no expected serious adverse events (SAEs) in this study. The
proposed procedures carry minimal risk to participants, and their care and comfort will be
ensured throughout. This research will be performed in accordance with the International
Conference on Harmonisation-Good Clinical Practice (ICH-GCP) standards. Research Ethics
Service ethical approval will be sought and confirmed before the start of the trial. The
study will be overseen by a steering committee who will act as the data-monitoring committee
to consider adverse effects and/or lack of adherence to the protocol.
Sample Size: As this was a feasibility study, a sample size calculation was not performed.
The study aimed to recruit 50 patients randomized (1:1) to control group (usual
rehabilitation and circadian rhythm study) or intervention group (usual rehabilitation
program + sleep circadian intervention program-SCIP) in patients under rehabilitation
treatment by musculoskeletal chronic pain on the opioids consumption. Data from key outcome
measures were later used to determine the sample size for a definitive trial.
Statistical analysis: Descriptive statistics of mean (standard deviation) or median
[interquartile range (IQR)] were estimated for quantitative variables with a normal or
non-normal distribution, respectively, while absolute and relative frequencies were used for
qualitative variables. Normal distribution was analysed using the Shapiro-Wilks test.
Participant characteristics were compared using Student's test, analysis of variance (ANOVA),
or non-parametric Mann-Whitney and Kruskal-Wallis tests for non-normal distribution. The
statistical level of significance was fixed at 0.05. All analyses were performed using R
statistical software, version 3.4.2.
