Improving Pain Management Via Spinal Cord Stimulation and Blood Pressure Reduction

NCT04676399 | Active Not Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 00146604
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Pain; Hypertension; Diuretics Drug Reactions; SCS

Outcome Measures

Primary Outcomes (19)

• 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)

Study Arms (2)

Hydrochlorothiazide Pill (12.5 mg twice a day)

EXPERIMENTAL

Planned use in this study 1. Condition/disease indication(s): Hypertension 2. Subject population: Chronic pain 3. Dose(s): 12.5 mg twice per day for 14 days. 4. Administration: Oral 5. Dosing regimen: 12.5 mg twice per day

Drug: Hydrochlorothiazide 12.5mg

Placebo

PLACEBO COMPARATOR

Has no active ingredients but is made to look like the study drug. 2 pills/day for 14 days.

Drug: Placebo

Interventions

Hydrochlorothiazide 12.5mg DRUG

2 pills/day (1 pill every morning and 1 pill every evening) for 14 days.

Also known as: HCTZ

Hydrochlorothiazide Pill (12.5 mg twice a day)

Placebo DRUG

2 pills/day (1 pill every morning and 1 pill every evening) for 14 days

Placebo

Eligibility Criteria

• Age: 40 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

The Marc A. Asher Comprehensive Spine Center at the Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Chronic Pain; Hypertension

Interventions

Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Seth W Holwerda, PhD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomization to either hydrochlorothiazide or placebo using a crossover study design will occur via a 1:1 ratio determined by computer generated randomization
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Mixed Model 2-way analysis of variance to asses pain and BP responses to the diuretic vs. placebo.

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: December 21, 2020
• Study Start: February 8, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 5, 2025

Record last verified: 2025-09

Locations

US (1)