Pancreatic Quantitative Sensory Testing (P-QST) to Predict Treatment Response for Pain in Chronic Pancreatitis

Study Overview
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Brief Summary
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Abdominal pain in chronic pancreatitis (CP) affects up to 90% of patients during the course of their disease, and response to currently available therapies is suboptimal and unpredictable. The proposed clinical trial will evaluate the predictive capability of Pancreatic Quantitative Sensory Testing (P-QST) - a novel assessment of neurosensory phenotyping- for improvement in pain in patients with CP who are undergoing medically-indicated invasive treatment with endoscopic therapy or surgery.

Detailed Description
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P-QST has been shown to be able to phenotype patients with CP into nociceptive patterns according to degree of central sensitization. As a tool to identify baseline nociceptive pattern in patients with painful CP, P-QST will be performed at baseline prior to planned invasive treatment with endoscopic therapy or decompressive surgery. We will evaluate the ability of P-QST to predict response to invasive treatment for painful CP, and to develop a predictive model for individualized prediction of treatment response. Patients will undergo pre-procedure P-QST testing before undergoing scheduled invasive treatment as directed by their treating gastroenterologist. The date of first endoscopic therapy or surgery will be used to calculate follow-up timepoints, which will be scheduled at 3, 6, and 12 months after the first endotherapy session or surgery. At each follow-up time point, patients will answer questions about their pain. In addition, patients will complete patient reported outcome tools (HADS, PCS instruments) and the Patient Global Impression of Change. Serum and urine samples will be obtained at baseline and at 6-month follow-up timepoints.

Official Title
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Pancreatic Quantitative Sensory Testing (P-QST) to Predict Treatment Response for Pain in Chronic Pancreatitis

Conditions
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Chronic Pancreatitis, Chronic Pain

Intervention / Treatment
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* Diagnostic Test: Quantitative Sensory Test 1
* Diagnostic Test: Quantitative Sensory Test 2
* Diagnostic Test: Quantitative Sensory Test 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients ≥ 18 years of age with definite CP undergoing decompressive invasive treatments (endoscopic therapy or surgery) to relieve main pancreatic duct obstruction due to stones and/or stricture for management of pain. Endoscopic therapy: Endoscopic Retrograde Cholangiopancreatography (ERCP) with pancreatic duct stone removal, stent placement, and/or stricture dilation, ± intraductal lithotripsy or Extracorporeal Shock Wave Lithotripsy (ESWL). Surgery: drainage procedures (Frey and Puestow operations) Exclusion Criteria: Patients with chronic pain from conditions other than CP Patients < 18 years of age Patients who have had endoscopic therapy within the past 12 months Patients who have undergone prior pancreatic surgery Patients who have resective surgical procedure planned (eg. Whipple procedure, Total Pancreatectomy) Patients with peripheral sensory deficits Patients with known pregnancy at the time of study screening** Note: Women who become pregnant during the course of the study can no longer participate in P-QST testing.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Interventional Model Description: Participants are assessed at baseline for nociceptive pattern via P-QST and followed longitudinally for the duration of the study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pancreatic Quantitative Sensory Testing (P-QST)<br>Definite Chronic Pancreatitis patients undergoing decompressive invasive treatments (endoscopic therapy or surgery) to relieve main pancreatic duct obstruction due to stones and/or stricture for management of pain will undergo P-QST prior to clinically-indicated invasive treatment. | Diagnostic Test: Quantitative Sensory Test 1<br>* Subject will give pain rating (on Visual Analogue Scale (VAS) 0-10) of single as well as multiple stimulation with round-tip non-invasive pin-prick device. Difference is recorded as Temporal Summation Score.<br>* Other names: Temporal Summation;Diagnostic Test: Quantitative Sensory Test 2<br>* Subject will state when they first detect pain and pain detection threshold in response to pressure administration with pressure algometer. Pressure threshold recorded in kilopascals(kP). Stimulation will be repeated in pancreatic and control dermatomes. Subject will then state pain tolerance threshold at same locations. Sensitization will be characterized by ratio of pancreatic vs. control dermatome scores.<br>* Other names: Pressure Threshold Testing;Diagnostic Test: Quantitative Sensory Test 3<br>* Subject will apply dominant hand to ice-chilled water bath (36F) for up to 2 minutes. Pain score (VAS 0-10) will be assessed each 10 seconds. Pain tolerance threshold (in kP) will be assessed with algometer on non-dominant thigh before and after water bath to determine change in threshold. Difference in pain tolerance recorded as Conditioned Pain Modulation Score.<br>* Other names: Conditioned Pain Modulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Pain Score | The primary outcome of the study is average pain score at 6 months post-procedure based on single-question numeric rating scale (NRS) (Scale of 0 to 10 how intense abdominal pain has been on average over the past 7 days (Scale: 0=No pain, 10=Worst pain Imaginable.) | six months post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Seven Day Pain Diary Score | The 7-day pain diary average score at 3 months after intervention. (Scale 0 = no pain to 10 = worst pain imaginable) | 3 months after intervention. | 
| Change from baseline in Seven Day Pain Diary Score | The 7-day pain diary average score at 6 months after intervention. (Scale 0 = no pain to 10 = worst pain imaginable) | 6 months after intervention. | 
| Change from baseline in Seven Day Pain Diary Score | The 7-day pain diary average score at 12 months after intervention. (Scale 0 = no pain to 10 = worst pain imaginable) | 12 months after intervention. | 
| Change from baseline in Single-question NRS score | Single-question NRS at 3 months after intervention (Scale 0 = no pain to 10 = worst pain imaginable) | at 3 months after intervention | 
| Change from baseline in Single-question NRS score | Single-question NRS at 12 months after intervention (Scale 0 = no pain to 10 = worst pain imaginable) | at 12 months. | 
| Number of patients using prescription opioids for pain control at time of assessment | Opioid use (yes,no binary answer) at 3 months. | 3 months | 
| Number of patients using prescription opioids for pain control at time of assessment | Opioid use (yes,no) at 6 months. | 6 months | 
| Number of patients using prescription opioids for pain control at time of assessment | Opioid use (yes,no) at 12 months. | 12 months | 
| Mean reported daily opioid dose for patients using prescription opioids at time of assessment | Opioid dose (continuous variable in milligrams of morphine equivalent) at 3 months. | 3 months | 
| Mean reported daily opioid dose for patients using prescription opioids at time of assessment | Opioid dose (continuous variable in milligrams of morphine equivalent) at 6 months. | 6 months | 
| Mean reported daily opioid dose for patients using prescription opioids at time of assessment | Opioid dose (continuous variable in milligrams of morphine equivalent) at 12 months. | 12 months | 
| Pain relief of ≥30% | Percentage of patients with ≥30% at 3 months after intervention | 3 months | 
| Pain relief of ≥30% | Percentage of patients with ≥30% at 6 months after intervention | 6 months | 
| Pain relief of ≥30% | Percentage of patients with ≥30% at 12 months after intervention | 12 months | 
| Pain relief of ≥50% | Percentage of patients with ≥50% at 3 months after intervention. | 3 months after intervention | 
| Pain relief of ≥50% | Percentage of patients with ≥50% at 6 months after intervention. | 6 months after intervention | 
| Pain relief of ≥50% | Percentage of patients with ≥50% at 12 months after intervention. | 12 months after intervention | 
| Change from baseline on the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale | The PROMIS Global Health Questionnaire is a validated self-reported tool that scores both mental and physical health at the time of assessment. Possible scores for both Mental and Physical Health range from 7 to 35 (lower score corresponds to poorer physical or mental health). | Baseline, 3, 6, and 12 months | 
| Change from baseline on the Patient Reported Outcomes Measurement Information System (PROMIS) Neuropathic Pain Scale | The PROMIS Global Health Questionnaire is a validated self-reported tool that scores neuropathic pain characteristics at the time of assessment. Possible scores range from 5 to 25 (higher score corresponds to more neuropathic pain characteristics). | Baseline, 3, 6, and 12 months | 
| Change from baseline on the Patient Reported Outcomes Measurement Information System (PROMIS) Nociceptive Pain Scale | The PROMIS Global Health Questionnaire is a validated self-reported tool that scores nociceptive pain characteristics at the time of assessment. Possible scores range from 5 to 25 (higher score corresponds to more nociceptive pain characteristics). | Baseline, 3, 6, and 12 months | 
| Change from baseline on the Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference Scale | The PROMIS Global Health Questionnaire is a validated self-reported tool that scores pain interference with aspects of daily life at the time of assessment. Possible scores range from 6 to 30 (higher score corresponds to more pain interference with daily activities). | Baseline, 3, 6, and 12 months | 
| Patient Global Impression of Change (PGIC) Scale | The PGIC is a validated self-reported tool that scores the patient's impression of change from baseline of their pain and overall health. Possible scores range from 1 to 7 (higher score corresponds to improvement). | 3, 6, and 12 months | 
| Change from baseline on the Pain Catastrophizing Scale (PCS) | The PCS is a validated self-reported tool that scores the patient tendency to catastrophize about pain or potential pain. Possible scores range from 0 to 42 (higher scores reflect more catastrophizing tendencies). | Baseline, 3, 6, and 12 months | 
| Change from baseline on the Hospital Anxiety and Depression Scale (HADS) | The HADS is a validated self-reported tool that screens for symptoms of anxiety and depression. Possible scores range from 0 to 21 (higher scores reflect more severe symptoms of anxiety or depression). | Baseline, 3, 6, and 12 months | 
| Change from baseline on the Modified Brief Pain Inventory Short Form (mBPI-SF) | The mBPI-SF is a validated self-reported tool that evaluates pain severity and pain interference with daily activities at the time of assessment. Possible scores for pain severity range from 0 to 40 (higher scores reflect more severe pain); possible scores for pain interference range from 0 to 70 (higher scores reflect more pain interference with daily life). | Baseline, 3, 6, and 12 months | 
| Change from baseline on the European Organization for the Research and Treatment of Cancer Quality(EORTC) of Life Questionnaire (QLQ) Core 30 (C30) | The EORTC QLQ-C30 is a validated self-reported tool measuring quality of life that reports scores on global health (quality of life), functioning (physical, role, emotional, cognitive, social), and symptoms (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties). All scores range from 0 to 100. A high score on quality of life indicates higher quality of life; a high score on a functioning scale indicates a higher level of functioning, and a high score on a symptom scale indicates a higher level of symptoms. | Baseline, 3, 6, and 12 months | 
| Change from baseline on the Comprehensive Pain Assessment Tool for Pancreatitis Short Form (COMPAT-SF) | The COMPAT-SF is a validated self-reported tool specifically designed for patients with pancreatic disease. Scores for pain severity (average, worst, and least) range from 0 to 10 (higher corresponds to more pain); scores for pain triggers (including food, exercise, and thermal changes) are scored on a scale from never to always (never, rarely, sometimes, very often, always); scores for pain symptom characteristics (cramping, shooting, stabbing) are scored on a scale from 0 (none) to 10 (worst possible). | Baseline, 3, 6, and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Pain, Chronic Pancreatitis, Recurrent Acute Pancreatitis, Chronic Abdominal Pain, ERCP, Pancreatic Surgery