Intrathecal Morphine Microdose Method Sensory Changes

Study Overview
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Brief Summary
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Following the retrospective study on the effectiveness of the microdose method of intrathecal morphine therapy, the investigators are interested in measuring the sensory changes at 4 time points during the microdose method. The microdose method involves weaning the patient off oral opioids and maintaining an opioid-free period prior to initiating a very low opioid dose in intrathecal therapy. The microdose method is a standard of care. The study involves measuring sensory changes to hot, cold, and pressure. Data collection will be performed at regularly scheduled clinic visits, examining range of doses, pain scores,dose escalations, quantifiable psychosocial factors ( not captured in previous retrospective study), and changes in sensory thresholds.

Detailed Description
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The use of intrathecal drug delivery systems for the management of chronic non-cancer pain has been in practice for over 30 years. A recently published study from the University of Texas Medical Branch performed a retrospective review on the morphine microdose method in community-based clinics. The goal of the study was to examine the morphine microdose method in an outpatient setting and assess success of therapy, pain scores and dose escalation. Patients were successfully weaned off their systemic opioids, maintained in an opioid-free period for 4-6 weeks, and then underwent a microdose trial and implantation. The majority of patients were successfully managed on morphine monotherapy, with a significant reduction in pain scores, and dose escalations comparable to prior studies. No prospective studies have examined the microdose method in correlation with changes in pain sensitivity. Several studies have looked at the use of various pain testing models to investigate the effects of chronic opioid therapy and changes in pain perception. A systematic review of the literature identified clinical studies incorporating measures of hyperalgesia in patients on chronic opioid therapy. This review was aimed at finding the optimal testing modality to evaluate pain threshold and tolerance to external stimuli, including mechanical (pressure, touch, injection), thermal (cold/heat), and electrical. Although the results did not reveal any one method with sufficient power, several prospective studies evaluating hyperalgesia with heat pain ratings have shown some promising results; two studies revealing significant changes in heat responses for opioid treatment groups, and one study demonstrating lower heat pain perception values following an opioid taper. The latter study of research pertaining to pain sensitivity changes following an opioid taper is lacking, and only recently was a study performed investigating changes in pressure threshold following transition from full mu agonist to buprenorphine. Little is known at this juncture how pain thresholds change due to opioid dose changes and/or route of delivery changes such as oral to intrathecal routes.

Official Title
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Intrathecal Morphine Microdose Method Sensory Changes: A Pilot Study

Conditions
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Analgesic Drug Dependence, Sensory Disorders, Chronic Pain

Intervention / Treatment
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* Behavioral: Quantitative Sensory Tests
* Behavioral: surveys


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 75 Selected for microdose Intrathecal pump therapy by their pain physician Chronic pain for at least 3 months Willing to cooperate with all study procedures Exclusion Criteria: Presence of cancer Age less than 18 years old or greater than 75 Current intrathecal therapy and/or with multiple intrathecal drugs (such as other opioids, local anesthetics, muscle relaxants) Medical conditions (myocardial infarction within the last year, uncontrolled diabetes, autoimmune disease Recent history of alcohol or substance abuse in the last 5 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: The study will be a non-randomized prospective trial. Participants will be selected for microdose intrathecal pump therapy by their pain physicians. Eligible participants will undergo an opioid taper by their physicians, and sensory tests will be carried out in the various stages of the intrathecal microdose treatment process (pre-taper, mid-taper, post-taper and post-implant phase).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intrathecal Pump Therapy Participants<br>Patients eligible for intrathecal pump therapy will undergo quantitative sensory tests and surveys during various stages of the treatment process. | Behavioral: Quantitative Sensory Tests<br>* Three testing modalities will be utilized for this study: Hot threshold test: The hot threshold method we will be utilizing has been described in the literature with good reproducibility and reliability. We will be using a similar system and have reproduced the program using a non-invasive device. Cold threshold test: the same non-invasive device will be used to test cold detection and pain threshold levels. This method is previously described. Pressure threshold: Mechanical testing (pressure pain threshold) will be assessed utilizing an algometer. We have used this method in a previous study and published results.<br>Behavioral: surveys<br>* surveys including anxiety, depression, pain behavior, fatigue, pain interference, physical function, sleep disturbance, self-efficacy, satisfaction roles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heat threshold measurements | Heat threshold measurements (degrees Celsius) will be obtained using a pen-shaped temperature probe. Tests will be performed on a designated painful and non-painful body surface. Testing will completed when patient reports numeric pain rating of 5 or greater, or at a temperature >49 degrees Celsius. | 2 years | 
| Cold threshold measurements | Cold threshold measurements (degrees Celsius) will be obtained using a pen-shaped temperature probe. Tests will be performed on a designated painful and non-painful body surface. Testing will be completed when patient reports discomfort with cold stimulus, or if probe temperature reaches 0 degrees Celsius. | 2 years | 
| Pressure threshold measurements | Pressure threshold measurements (Newtons) will be obtained using a hand-held algometer. Tests will be performed on a designated painful and non-painful body surface. Testing will be completed when patient reports discomfort with pressure stimulus, or if pressure exceeds 60 Newtons. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demographic Evaluation - Pain History | To describe the patient population and to evaluate patient factors, which predict successful trials. The investigators will do a chart review of one year prior to start of the trial to examine the pain history. | 2 years | 
| Demographic Evaluation - Medical History | To describe the patient population and to evaluate patient factors, which predict successful trials. The investigators will do a chart review of one year prior to start of the trial to examine the medical history. | 2 years | 
| Demographic Evaluation - Body Mass Index | To describe the patient population and to evaluate patient factors, which predict successful trials. The investigators will collect data on body mass index. | 2 years | 
| Demographic Evaluation - Gender | To describe the patient population and to evaluate patient factors, which predict successful trials. The investigators will collect data on gender. | 2 years | 
| Demographic Evaluation - Surgical History | To describe the patient population and to evaluate patient factors, which predict successful trials. We will do a chart review of one year prior to start of the trial to examine the surgical history. | 2 years | 
| Demographic Evaluation - Age | To describe the patient population and to evaluate patient factors, which predict successful trials. The investigators will collect data on patient age. | 2 years | 
| Demographic Evaluation - Social History | To describe the patient population and to evaluate patient factors, which predict successful trials. We will do a chart review of one year prior to start of the trial to examine the social history. | 2 years | 
| Demographic Evaluation - Urine Drug Tests | To describe the patient population and to evaluate patient factors, which predict successful trials. We will do a chart review of one year prior to start of the trial to examine the urine drug tests | 2 years | 
| Demographic Evaluation - Numeric Pain Scale Scores | To describe the patient population and to evaluate patient factors, which predict successful trials. We will do a chart review of one year prior to start of the trial to examine numeric pain scale scores. | 2 years | 
| surveys - Anxiety | Patient-Reported Outcomes Measurement Information System survey on anxiety will be administered at the subject's initial, halfway and end of their evaluations. The results from the surveys will be aggregated and compared to other participants' responses. | 2 years | 
| surveys - Depression | Patient-Reported Outcomes Measurement Information System survey on depression will be administered at the subject's initial, halfway and end of their evaluations. The results from the surveys will be aggregated and compared to other participants' responses. | 2 years | 
| surveys - Pain Behavior | Patient-Reported Outcomes Measurement Information System survey on pain behavior will be administered at the subject's initial, halfway and end of their evaluations. The results from the surveys will be aggregated and compared to other participants' responses. | 2 years | 
| surveys - Fatigue | Patient-Reported Outcomes Measurement Information System survey on fatigue will be administered at the subject's initial, halfway and end of their evaluations. The results from the surveys will be aggregated and compared to other participants' responses. | 2 years | 
| surveys - Pain Interference | Patient-Reported Outcomes Measurement Information System survey on pain interference will be administered at the subject's initial, halfway and end of their evaluations. The results from the surveys will be aggregated and compared to other participants' responses. | 2 years | 
| surveys - Physical Function | Patient-Reported Outcomes Measurement Information System survey on physical function will be administered at the subject's initial, halfway and end of their evaluations. The results from the surveys will be aggregated and compared to other participants' responses. | 2 years | 
| surveys - Sleep Disturbance | Patient-Reported Outcomes Measurement Information System survey on sleep disturbance will be administered at the subject's initial, halfway and end of their evaluations. The results from the surveys will be aggregated and compared to other participants' responses. | 2 years |