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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypertension; Chronic Pain; Diuretics Drug Reactions; SCS
• Intervention / Treatment: Drug: Hydrochlorothiazide 12.5mg; Drug: Placebo

Detailed Description

The goal of the PASSION study is to determine the extent to which reductions in blood pressure improve pain management via SCS

1. 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.
2. 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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The Marc A. Asher Comprehensive Spine Center at the Kansas University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or Female, age 40-79
2. Chronic low back pain
3. Permanent spinal cord stimulator implant for chronic pain
4. Stage 1 hypertension (BP 130-139/80-89 mmHg) with ASCVD risk ≥10%
5. Stage 2 hypertension (BP ≥ 140/90 mmHg)
6. Willing to visit research lab (Fairway CTSU)
7. Willing to undergo a blood draw
8. Able to provide written informed consent

Exclusion Criteria:

1. Any history of abnormal responses (allergy) to thiazide-type drugs
2. Currently taking any antihypertensive medication
3. Stage 1 hypertension (BP 130-139/80-89 mmHg) with ASCVD risk <10%
4. BP ≥160/100 (these patients should be promptly treated with 2 medications)
5. Secondary hypertension (e.g., aldosteronism, renal artery stenosis)
6. Symptomatic hypotension (weakness or syncope upon standing)
7. Renal failure
8. Diabetes requiring insulin or glucose-lowering drugs
9. History of neurological disease (e.g., dementias, Parkinson's)
10. History of stroke
11. Current diagnosis of cancer
12. Women who are pregnant or planning to become pregnant
13. Any active infection
14. Subject is unwilling or unable to comply with the protocol
15. If currently taking a NSAID, willing to stop for at least 3 days prior to beginning study and throughout study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hydrochlorothiazide Pill (12.5 mg twice a day); 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; 2 pills/day (1 pill every morning and 1 pill every evening) for 14 days.; Other Names: HCTZ
Placebo Comparator: Placebo; Has no active ingredients but is made to look like the study drug. 2 pills/day for 14 days.	Drug: Placebo; 2 pills/day (1 pill every morning and 1 pill every evening) for 14 days

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Seth W Holwerda, PhD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 19, 2020
• First Submitted That Met QC Criteria: December 14, 2020
• First Posted (Actual): December 21, 2020

Study Record Updates

• Last Update Posted (Estimated): September 5, 2025
• Last Update Submitted That Met QC Criteria: September 3, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Hypertension; Chronic Pain; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Substandard Drugs; Pharmaceutical Preparations; Sulfonamides; Sulfones; Chlorothiazide; Benzothiadiazines; Thiazides; Hydrochlorothiazide; Counterfeit Drugs
• Other Study ID Numbers: 00146604

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD may be available upon reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes