Improving Pain Management Via Spinal Cord Stimulation and Blood Pressure Reduction

Study Overview
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Brief Summary
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The purpose of this study (PASSION study) is to monitor symptoms of chronic pain before and after 2 weeks of a standard drug commonly used to treat elevated blood pressure compared with 2 weeks of placebo (crossover design) so that we may better understand how blood pressure affects your level of pain. This study is not testing an experimental drug.

Detailed Description
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The goal of the PASSION study is to determine the extent to which reductions in blood pressure improve pain management via SCS Examine the extent to which reductions in blood pressure (2 weeks of diuretic and 2 weeks of placebo) improve pain management among patients with chronic pain and hypertension compared. Examine the extent to which arterial baroreflex function, which is critical to blood pressure regulation, is impaired in patients with chronic pain and hypertension and is correlated with chronic pain symptoms.

Official Title
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Improving Pain Management Via Spinal Cord Stimulation and Blood Pressure Reduction (PASSION Study)

Conditions
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Chronic Pain, Hypertension, Diuretics Drug Reactions, SCS

Intervention / Treatment
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* Drug: Hydrochlorothiazide 12.5mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female, age 40-79 Chronic low back pain Permanent spinal cord stimulator implant for chronic pain Stage 1 hypertension (BP 130-139/80-89 mmHg) with ASCVD risk ≥10% Stage 2 hypertension (BP ≥ 140/90 mmHg) Willing to visit research lab (Fairway CTSU) Willing to undergo a blood draw Able to provide written informed consent Exclusion Criteria: Any history of abnormal responses (allergy) to thiazide-type drugs Currently taking any antihypertensive medication Stage 1 hypertension (BP 130-139/80-89 mmHg) with ASCVD risk <10% BP ≥160/100 (these patients should be promptly treated with 2 medications) Secondary hypertension (e.g., aldosteronism, renal artery stenosis) Symptomatic hypotension (weakness or syncope upon standing) Renal failure Diabetes requiring insulin or glucose-lowering drugs History of neurological disease (e.g., dementias, Parkinson's) History of stroke Current diagnosis of cancer Women who are pregnant or planning to become pregnant Any active infection Subject is unwilling or unable to comply with the protocol If currently taking a NSAID, willing to stop for at least 3 days prior to beginning study and throughout study

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 79 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Mixed Model 2-way analysis of variance to asses pain and BP responses to the diuretic vs. placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hydrochlorothiazide Pill (12.5 mg twice a day)<br>Planned use in this study Condition/disease indication(s): Hypertension Subject population: Chronic pain Dose(s): 12.5 mg twice per day for 14 days. Administration: Oral Dosing regimen: 12.5 mg twice per day | Drug: Hydrochlorothiazide 12.5mg<br>* 2 pills/day (1 pill every morning and 1 pill every evening) for 14 days.<br>* Other names: HCTZ;|
| Placebo Comparator: Placebo<br>Has no active ingredients but is made to look like the study drug. 2 pills/day for 14 days. | Drug: Placebo<br>* 2 pills/day (1 pill every morning and 1 pill every evening) for 14 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Blood Pressure Measurement From Visit 1 to Visit 2 | Measurements of blood pressure via arm cuff and finger cuff | 1 week | 
| Change in Blood Pressure Measurement From Visit 2 to Visit 3 | Measurements of blood pressure via arm cuff and finger cuff | 1 week | 
| Change in Blood Pressure Measurement From Visit 3 to Visit 4 | Measurements of blood pressure via arm cuff and finger cuff | 1 week | 
| Change in Blood Pressure Measurement From Visit 4 to Visit 5 | Measurements of blood pressure via arm cuff and finger cuff | 2 week | 
| Change from Visit 1 PainDETECT Questionnaire to Visit 2 | A battery of questionnaires is intended to understand key aspects of pain, mood, and function as quickly and efficiently as possible. The focus of these measures is on obtaining an accurate assessment of pain, while also asking about physical function, anxiety, and other associated somatic disturbances. These questionnaires will be taken prior to SCS implant (Baseline) and after SCS implant (1 week post-op, 4 weeks post-op, and 8 weeks post-op ) to assess and compare. Neuropathic Pain Descriptors: The Pain DETECT is a 9-item measure of sensory descriptors and spatial and temporal characteristics that has demonstrated utility in identifying central neuropathic pain. | 1 week | 
| Change from Visit 2 PainDETECT Questionnaire to Visit 3 | A battery of questionnaires is intended to understand key aspects of pain, mood, and function as quickly and efficiently as possible. The focus of these measures is on obtaining an accurate assessment of pain, while also asking about physical function, anxiety, and other associated somatic disturbances. These questionnaires will be taken prior to SCS implant (Baseline) and after SCS implant (1 week post-op, 4 weeks post-op, and 8 weeks post-op ) to assess and compare. Neuropathic Pain Descriptors: The Pain DETECT is a 9-item measure of sensory descriptors and spatial and temporal characteristics that has demonstrated utility in identifying central neuropathic pain. | 1 week | 
| Change from Visit 3 PainDETECT Questionnaire to Visit 4 | A battery of questionnaires is intended to understand key aspects of pain, mood, and function as quickly and efficiently as possible. The focus of these measures is on obtaining an accurate assessment of pain, while also asking about physical function, anxiety, and other associated somatic disturbances. These questionnaires will be taken prior to SCS implant (Baseline) and after SCS implant (1 week post-op, 4 weeks post-op, and 8 weeks post-op ) to assess and compare. Neuropathic Pain Descriptors: The Pain DETECT is a 9-item measure of sensory descriptors and spatial and temporal characteristics that has demonstrated utility in identifying central neuropathic pain. | 1 week | 
| Change from Visit 4 PainDETECT Questionnaire to Visit 5 | A battery of questionnaires is intended to understand key aspects of pain, mood, and function as quickly and efficiently as possible. The focus of these measures is on obtaining an accurate assessment of pain, while also asking about physical function, anxiety, and other associated somatic disturbances. These questionnaires will be taken prior to SCS implant (Baseline) and after SCS implant (1 week post-op, 4 weeks post-op, and 8 weeks post-op ) to assess and compare. Neuropathic Pain Descriptors: The Pain DETECT is a 9-item measure of sensory descriptors and spatial and temporal characteristics that has demonstrated utility in identifying central neuropathic pain. | 2 week | 
| Visit 1 Catecholamines( Norepinephrine) & Tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL6) Blood Work | Catecholamines( Norepinephrine) Blood Test: pg/mL • normal range for norepinephrine is 70 to 1700 pg/mL Tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL6) Blood Test: pg/mL IL-6 normal values was 6-31 pg/mL TNF-α 5 pg/mL, | Visit 1 (Day 1) | 
| Visit 1 Lipid Panel Blood Work Results | Lipid panel Blood Test: mg/dL, Total Cholesterol Less than 170mg/dL Non-HDL Less than 120mg/dL LDL Less than 100mg/dL HDL More than 45mg/dL | Visit 1 (Day 1) | 
| Visit 1 Comprehensive Metabolic Panel Blood Work Results | Metabolic Panel Blood Test (Electrolyte Check): mg/dL, mmol/L , g/dL, U/L, mEq/L Albumin: 3.4 to 5.4 g/dL (34 to 54 g/L) Alkaline phosphatase: 20 to 130 U/L ALT (alanine aminotransferase): 4 to 36 U/L AST (aspartate aminotransferase): 8 to 33 U/L BUN (blood urea nitrogen): 6 to 20 mg/dL (2.14 to 7.14 mmol/L) Calcium: 8.5 to 10.2 mg/dL (2.13 to 2.55 mmol/L) Chloride: 96 to 106 mEq/L (96 to 106 mmol/L) CO2 (carbon dioxide): 23 to 29 mEq/L (23 to 29 mmol/L) Creatinine: 0.6 to 1.3 mg/dL (53 to 114.9 µmol/L) Glucose: 70 to 100 mg/dL (3.9 to 5.6 mmol/L) Potassium: 3.7 to 5.2 mEq/L (3.70 to 5.20 mmol/L) Sodium: 135 to 145 mEq/L (135 to 145 mmol/L) Total bilirubin: 0.1 to 1.2 mg/dL (2 to 21 µmol/L) Total protein: 6.0 to 8.3 g/dL (60 to 83 g/L) | Visit 1 (Day 1) | 
| Visit 1 Stored Plasma Blood Work Results | Stored plasma for inflammatory markers | Visit 1 (Day 1) | 
| Visit 2 Comprehensive Metabolic Panel/Electrolyte Check Blood Work Results | Metabolic Panel Blood Test (Electrolyte Check): mg/dL, mmol/L , g/dL, U/L, mEq/L Albumin: 3.4 to 5.4 g/dL (34 to 54 g/L) Alkaline phosphatase: 20 to 130 U/L ALT (alanine aminotransferase): 4 to 36 U/L AST (aspartate aminotransferase): 8 to 33 U/L BUN (blood urea nitrogen): 6 to 20 mg/dL (2.14 to 7.14 mmol/L) Calcium: 8.5 to 10.2 mg/dL (2.13 to 2.55 mmol/L) Chloride: 96 to 106 mEq/L (96 to 106 mmol/L) CO2 (carbon dioxide): 23 to 29 mEq/L (23 to 29 mmol/L) Creatinine: 0.6 to 1.3 mg/dL (53 to 114.9 µmol/L) Glucose: 70 to 100 mg/dL (3.9 to 5.6 mmol/L) Potassium: 3.7 to 5.2 mEq/L (3.70 to 5.20 mmol/L) Sodium: 135 to 145 mEq/L (135 to 145 mmol/L) Total bilirubin: 0.1 to 1.2 mg/dL (2 to 21 µmol/L) Total protein: 6.0 to 8.3 g/dL (60 to 83 g/L) | Visit 2 (Day 7) | 
| Visit 3 Comprehensive Metabolic Panel/Electrolyte Check Blood Work Results | Metabolic Panel Blood Test (Electrolyte Check): mg/dL, mmol/L , g/dL, U/L, mEq/L Albumin: 3.4 to 5.4 g/dL (34 to 54 g/L) Alkaline phosphatase: 20 to 130 U/L ALT (alanine aminotransferase): 4 to 36 U/L AST (aspartate aminotransferase): 8 to 33 U/L BUN (blood urea nitrogen): 6 to 20 mg/dL (2.14 to 7.14 mmol/L) Calcium: 8.5 to 10.2 mg/dL (2.13 to 2.55 mmol/L) Chloride: 96 to 106 mEq/L (96 to 106 mmol/L) CO2 (carbon dioxide): 23 to 29 mEq/L (23 to 29 mmol/L) Creatinine: 0.6 to 1.3 mg/dL (53 to 114.9 µmol/L) Glucose: 70 to 100 mg/dL (3.9 to 5.6 mmol/L) Potassium: 3.7 to 5.2 mEq/L (3.70 to 5.20 mmol/L) Sodium: 135 to 145 mEq/L (135 to 145 mmol/L) Total bilirubin: 0.1 to 1.2 mg/dL (2 to 21 µmol/L) Total protein: 6.0 to 8.3 g/dL (60 to 83 g/L) | Visit 3 (Day 14) | 
| Visit 4 Comprehensive Metabolic Panel/Electrolyte Check Blood Work Results | Metabolic Panel Blood Test (Electrolyte Check): mg/dL, mmol/L , g/dL, U/L, mEq/L Albumin: 3.4 to 5.4 g/dL (34 to 54 g/L) Alkaline phosphatase: 20 to 130 U/L ALT (alanine aminotransferase): 4 to 36 U/L AST (aspartate aminotransferase): 8 to 33 U/L BUN (blood urea nitrogen): 6 to 20 mg/dL (2.14 to 7.14 mmol/L) Calcium: 8.5 to 10.2 mg/dL (2.13 to 2.55 mmol/L) Chloride: 96 to 106 mEq/L (96 to 106 mmol/L) CO2 (carbon dioxide): 23 to 29 mEq/L (23 to 29 mmol/L) Creatinine: 0.6 to 1.3 mg/dL (53 to 114.9 µmol/L) Glucose: 70 to 100 mg/dL (3.9 to 5.6 mmol/L) Potassium: 3.7 to 5.2 mEq/L (3.70 to 5.20 mmol/L) Sodium: 135 to 145 mEq/L (135 to 145 mmol/L) Total bilirubin: 0.1 to 1.2 mg/dL (2 to 21 µmol/L) Total protein: 6.0 to 8.3 g/dL (60 to 83 g/L) | Visit 4 (Day 21) | 
| Visit 5 Comprehensive Metabolic Panel/Electrolyte Check Blood Work Results | Metabolic Panel Blood Test (Electrolyte Check): mg/dL, mmol/L , g/dL, U/L, mEq/L Albumin: 3.4 to 5.4 g/dL (34 to 54 g/L) Alkaline phosphatase: 20 to 130 U/L ALT (alanine aminotransferase): 4 to 36 U/L AST (aspartate aminotransferase): 8 to 33 U/L BUN (blood urea nitrogen): 6 to 20 mg/dL (2.14 to 7.14 mmol/L) Calcium: 8.5 to 10.2 mg/dL (2.13 to 2.55 mmol/L) Chloride: 96 to 106 mEq/L (96 to 106 mmol/L) CO2 (carbon dioxide): 23 to 29 mEq/L (23 to 29 mmol/L) Creatinine: 0.6 to 1.3 mg/dL (53 to 114.9 µmol/L) Glucose: 70 to 100 mg/dL (3.9 to 5.6 mmol/L) Potassium: 3.7 to 5.2 mEq/L (3.70 to 5.20 mmol/L) Sodium: 135 to 145 mEq/L (135 to 145 mmol/L) Total bilirubin: 0.1 to 1.2 mg/dL (2 to 21 µmol/L) Total protein: 6.0 to 8.3 g/dL (60 to 83 g/L) | Visit 5 (Day 28) | 
| Visit 5 Lipid Panel Blood Work Results | Lipid panel Blood Test: mg/dL, Total Cholesterol Less than 170mg/dL Non-HDL Less than 120mg/dL LDL Less than 100mg/dL HDL More than 45mg/dL | Visit 5 (Day 28) | 
| Visit 5 Stored Plasma Blood Work Results | Stored plasma for inflammatory markers Blood Test | Visit 5 (Day 35) | 
| Visit 5 Catecholamines( Norepinephrine) & Tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL6) Blood Work | Catecholamines( Norepinephrine) Blood Test: pg/mL • normal range for norepinephrine is 70 to 1700 pg/mL Tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL6) Blood Test: pg/mL IL-6 normal values was 6-31 pg/mL TNF-α 5 pg/mL, | Visit 5 (Day 28) |