Physiological Study of the Efficacy and Mechanistic Effects of Alcohol Renal Denervation

NCT03465917 | Completed Early Phase 1 FDA Drug FDA Device

• 1 other identifier: STU 112014-023
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Hypertension is a major risk factor for heart disease and stroke, two of the leading causes of death in the United States. Hypertension is a common and widespread problem; unfortunately, current treatment strategies fail to adequately control blood pressure in up to 50% of patients either because of failure to take prescribed medications (because of cost, side effects, inconvenience etc.) or lack of therapeutic response. Indeed, it is estimated that 50% of patients stop taking antihypertensive medication within 6-12 months after the initiation of drug therapy. Despite enthusiasm for a novel approach called renal denercation, presently there are no integrative studies of the antihypertensive effect of renal denervation on the multiple regulatory pathways it may consequentially affect. Experimental evidence from pre-clinical models suggests the effects are due to reducing efferent sympathetic activity and thus lowering blood pressure by altering the renin-angiotensin system. Uncontrolled clinical studies in humans suggest that when effective, this procedure may also lower renal sympathetic nerve activity. However the sympathetic response to monopolar radiofrequency therapy has been highly variable. Moreover, there have been no assessments of procedural efficacy performed in humans. Thus the actual mechanism by which this type of procedure reduces BP in humans is largely unknown, making it extremely difficult to identify the appropriate patients for this invasive procedure. Recently, chemical renal denervation using ethanol (EtOH), was demonstrated to markedly lower blood pressure in small numbers of patients with resistant hypertension. However the mechanisms by which blood pressure is altered using this novel technique in humans is entirely unknown, and procedural efficacy has also not been assessed. Therefore it is unclear, whether in humans renal sympathetic nerve activity is lowered following renal denervation using this new approach. The Investigators propose to use high resolution physiological testing to determine the effects of chemical renal artery denervation on sympathetic activity. Therefore the global objective of this physiological study is to provide the first detailed assessment of the integrated mechanistic effects of chemical renal nerve denervation in humans with hypertension that is uncontrolled by conventional treatment (because of lack of adherence or response to therapy).

Conditions

Hypertension

Outcome Measures

Primary Outcomes (1)

• Renal sympathetic activity

  18F-Fluorodopamine scanning of the kidney

  Change in renal sympathetic activity at 8 weeks

Secondary Outcomes (4)

• Blood pressure

  Change in ambulatory blood pressure 24 hours, 1 week, 8 weeks, 6 months and 12 months after denervation.

• Muscle sympathetic activity

  Change in Muscle sympathetic nervous system activity 8 weeks, 6 months after renal denervation

• Vascular function

  Change in flow mediated dilation 8 weeks, 6 months after renal denervation

• Vascular stiffness

  Change in pulswave velocity at 8 weeks, 6 months after renal denervation

Study Arms (1)

Renal Denervation

EXPERIMENTAL

Renal denervation using the Peregrine Catheter for extravascular administration of ethanol

Combination Product: Renal Denervation

Interventions

Renal Denervation COMBINATION_PRODUCT

Bilateral denervation of the renal arteries using extravascular administration of neurolytic alcohol

Renal Denervation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient presents with treated or untreated hypertension.
• Adults aged 18-75 years, male or female
• Patient has a clinic systolic blood pressure \>140mmHg (average of 3 measurements), or \>135mmHg in patients with type II diabetes
• Patient has a daytime mean systolic blood pressure of ≥135 and diastolic blood pressure ≥85mHg based on 24 hours ambulatory blood pressure monitoring
• Investigator judges that the subject can be managed safely for up to 12 weeks (4 weeks run-in plus 8 weeks post-treatment) with the use of standard background regimen of losartan/hydrochlorothiazide; patients with true resistant hypertension will be required to maintaining current antihypertensive regime for the duration of the study.

You may not qualify if:

• Patient has known or suspected secondary hypertension
• Use of systemic drugs that may be used for the treatment of hypertension, for a non-hypertension indication for the trial, (e.g. atrial fibrillation/atrial flutter, heart failure, or calcium channel blocker for heart rate control).
• Renal artery stenosis ≥ 50% diameter stenosis, or aneurysm(s)
• Patients with atrial fibrillation.
• Patient has type 1 diabetes
• Patient has type 2 diabetes and evidence of peripheral neuropathy
• History of previous stenting or balloon angioplasty of the renal arteries.
• Untreated hypothyroid or hypo-parathyroid.
• Orthostatic hypotension defined as \>20 mmHg of systolic blood pressure and/or more than 10 mmHg in diastolic blood pressure fall after standing for 3mins
• Renal artery anatomy as assessed by imaging (CT-angiogram or, MR angiogram or renal angiogram) meeting the following criteria:
• Single renal artery or two renal arteries, if either has a diameter of \< 5 mm or \> 7 mm or a length of \< 11 mm,
• Accessory renal arteries with diameter \> 2.0 mm and \< 5.0 mm,
• Excessive renal artery tortuosity based on Investigator judgment,
• Moderate or severe, and diffuse renal artery calcification, and/or
• Renal anatomic renovascular abnormalities (as assessed by renal imaging) that would increase the risk of renal catheterization.

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

The Institute for Exercise and Environmental Medicine

Dallas, Texas, 75231, United States

Location

Related Publications (1)

• Hearon CMJ, Howden EJ, Fu Q, Yoo JK, Dias KA, Roberts-Reeves MA, Samels M, Sarma S, Nesbitt S, Vongpatanasin W, Goldstein DS, Addo T, Levine BD. Evidence of Reduced Efferent Renal Sympathetic Innervation After Chemical Renal Denervation in Humans. Am J Hypertens. 2021 Aug 9;34(7):744-752. doi: 10.1093/ajh/hpab022.

  PMID: 33677553 DERIVED

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2018
• First Posted: March 14, 2018
• Study Start: March 1, 2018
• Primary Completion: March 6, 2019
• Study Completion: November 12, 2019
• Last Updated: May 11, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)