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Neurobiological Mechanisms of Stress in Youth With Chronic Widespread Pain

Not Applicable
Recruiting
Conditions
Stress, Physiological
Chronic Widespread Pain
Stress, Psychological
Interventions
Diagnostic Test: functional Magnetic Resonance Imaging (fMRI)
Other: Allostatic Load Composite
Registration Number
NCT04488757
Lead Sponsor
Boston Children's Hospital
Brief Summary

Chronic widespread pain (CWP) is a common chronic pain condition in youth and often associated with significant pain-related and psychosocial impairment. Understanding the neurobiological mechanisms that may underlie pediatric chronic pain and pain-related impairment can inform future treatments to ameliorate patients' suffering, making it a critical area of empirical investigation.

Detailed Description

Pediatric chronic widespread pain (CWP) is a serious public health problem resulting in high levels of healthcare utilization and disability. Youth with CWP also frequently report exposure to adverse childhood experiences (ACEs; abuse/neglect, violent/conflictual home environment, etc.) and a significant subset continue to experience physical and psychosocial impairment long-term. Certain mind-body interventions such as mindfulness-based stress reduction (MBSR) or meditation may be particularly appropriate for youth with CWP as they have been shown to modulate stress-induced maladaptation of the HPA-axis, autonomic nervous system, cardiovascular system, and brain structure (e.g., hippocampus). However, it is currently unknown if these targets are affected in youth with CWP. Preliminary research indicates that allostatic load (AL), or "wear and tear" on the nervous system due to stress, may contribute to pain chronicity. Similarly, evidence suggests that the hippocampus, a brain structure that is among the most deleteriously affected by stress, plays a role in pain perception. However, no study to-date has examined AL and hippocampal functioning in relation to stress exposure in youth with CWP. Mind-body interventions such as MBSR or meditation are an important and safe therapy option for both pain and stress reduction in youth with CWP and may modulate the negative impact of ACEs, so there is a critical need to know if these mechanisms are engaged in this population. The current study utilizes multifactorial physiological and neuroimaging measurement techniques to enhance our understanding of the potential role of these mechanisms in pain-related impairment and responsiveness to mind-body interventions over time. The aims of this study are to better characterize AL, assessed via a multifactorial composite, and hippocampal functioning via fMRI in pediatric CWP as specific targets for mind-body interventions that can lead to treatment optimization and improved compliance.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
70
Inclusion Criteria
  • Between ages 11-17 years
  • Referred to the Boston Children's Hospital Pain Treatment Service for evaluation of a CWP condition with duration > 3 months
  • Right-handed
Exclusion Criteria
  • Inability to speak sufficient English to complete questionnaires
  • Severe cognitive impairment
  • Prescription steroidal (interference with cortisol measures) or psychotropic medication
  • Any other chronic pain diagnosis (e.g., migraines, abdominal pain, CRPS)
  • fMRI contraindications (e.g., dental appliances)

Healthy Control (HC) group:

Inclusion Criteria:

  • Between ages 11-17 years
  • Right-handed

Exclusion Criteria:

  • Inability to speak sufficient English to complete questionnaires
  • Severe cognitive impairment
  • Prescription steroidal (interference with cortisol measures) or psychotropic medication
  • Any chronic pain diagnosis
  • Presence of documented chronic (> 3 months) medical condition with an identifiable, organic cause (e.g., diabetes, cystic fibrosis)
  • fMRI contraindications (e.g., dental appliances)

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Study ArmAllostatic Load CompositeAll participants enrolled in the study will undergo baseline fMRI and baseline and follow-up (4-month post-baseline) assessment of stress physiology (i.e., allostatic load). Treatment as usual information will be gathered for all participants to assess observational intervention response.
Study Armfunctional Magnetic Resonance Imaging (fMRI)All participants enrolled in the study will undergo baseline fMRI and baseline and follow-up (4-month post-baseline) assessment of stress physiology (i.e., allostatic load). Treatment as usual information will be gathered for all participants to assess observational intervention response.
Primary Outcome Measures
NameTimeMethod
Change in Morning Cortisolbaseline and 4-month follow-up

measured via 2 samples of saliva taken via passive drool over the course of two days. After analysis, morning cortisol will be dichotomously coded with participants receiving a "1" if they score over one standard deviation above the mean. Coding will them be combined to formulate an allostatic load risk ratio, with higher scores indicating greater risk for allostatic load.

Change in Body-Mass Index (BMI)baseline and 4-month follow-up

measured via height and weight (in cm and kg) by a trained nurse. Results will be coded to capture individuals that score in the "underweight", "normal", "overweight" and "obese" ranges with individuals falling in all categories but "normal" receiving a coding of "1" to be included in the allostatic load risk ratio. Scoring of BMI ranges will be done using ezbmi- calculates deviation from expected BP/BMI by age/gender.

Change in Heart Rate (HR)baseline and 4-month follow-up

measured via pulse taken by a trained nurse. Results will be coded dichotomously with individuals scoring a "1" whose HR falls greater than or equal to one standard deviation above the mean of the sample. This scoring will also be included in the larger allostatic load risk ratio.

Hippocampal Functioningbaseline

measured via fMRI

Change in Dehydroepiandrosterone (DHEA)baseline and 4-month follow-up

measured via 2 samples of saliva taken via passive drool over the course of two days. After analysis, DHEA will be dichotomously coded with participants receiving a "1" if they score over one standard deviation above the mean. Coding will them be combined to formulate an allostatic load risk ratio, with higher scores indicating greater risk for allostatic load.

Change in Flattened Cortisolbaseline and 4-month follow-up

measured via 10 samples of saliva taken via passive drool over the course of two days. After analysis, the presence of cortisol will be dichotomously coded with participants receiving a "1" if the change in cortisol levels across the day fell at or below one standard deviation below the mean. Coding will them be combined to formulate an allostatic load risk ratio, with higher scores indicating greater risk for allostatic load.

Change in Waist-Hip Ratio (WHR)baseline and 4-month follow-up

measured via tape measure around the smallest part of the waist and the widest part of the hips by a trained research coordinator. Results (waist measurement/hip measurement) will be coded dichotomously with individuals scoring a "1" whose WHR falls greater than or equal to one standard deviation above the mean of the sample. This scoring will also be included in the larger allostatic load risk ratio.

Change in Blood Pressurebaseline and 4-month follow-up

measured via blood pressure cuff by trained nurse. Results will be coded to capture levels that fall in the "normal", "prehypertension" and "hypertension" range with individuals scoring in the latter two ranges receiving a coding of "1" to be included in the allostatic load risk composite measure. Scoring of blood pressure ranges will be done using ezbmi- calculates deviation from expected BP/BMI by age/gender.

Secondary Outcome Measures
NameTimeMethod
Change in Functional Disabilitybaseline and 4-month follow-up

measured via self-report Functional Disability Inventory (range: 0-60). Higher rating indicates greater functional disability.

Change in Pain Intensitybaseline and 4-month follow-up

measured via numeric rating scale (range: 0-10). Higher rating indicates more intense pain.

Change in Sleepbaseline and 4-month follow-up

measured via Patient Reported Outcome Measurement Information System (PROMIS) sleep disturbance scale short-form (8a). Raw scores are converted to T-scores (range: 0-100). Higher rating indicates greater impairment in sleep.

Trial Locations

Locations (1)

Boston Children's Hospital

🇺🇸

Boston, Massachusetts, United States

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