Hypertension Clinical Trial
Official title:
Physiological Study of the Efficacy and Mechanistic Effects of Alcohol Renal Denervation
Verified date | May 2020 |
Source | University of Texas Southwestern Medical Center |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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).
Status | Completed |
Enrollment | 5 |
Est. completion date | November 12, 2019 |
Est. primary completion date | March 6, 2019 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility |
9.1 Please indicate the inclusion criteria for enrollment: Six patients will participate in
this study. Patients who present with uncontrolled hypertension (classified as clinic
systolic blood pressure not at target level >140mmHg) to their primary care provider,
emergency room (ER), specialist hypertension clinic or urgent care center will be asked to
participate. Inclusion criteria include: 1. Patient presents with treated or untreated hypertension. 2. Adults aged 18-75 years, male or female 3. Patient has a clinic systolic blood pressure >140mmHg (average of 3 measurements), or >135mmHg in patients with type II diabetes 4. Patient has a daytime mean systolic blood pressure of =135 and diastolic blood pressure =85mHg based on 24 hours ambulatory blood pressure monitoring 5. 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. Exclusion Criteria. Any patient who meets any of the following exclusion criteria will not be eligible for the study. 1. Patient has known or suspected secondary hypertension 2. 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). 3. Renal artery stenosis = 50% diameter stenosis, or aneurysm(s) 4. Patients with atrial fibrillation. 5. Patient has type 1 diabetes 6. Patient has type 2 diabetes and evidence of peripheral neuropathy 7. History of previous stenting or balloon angioplasty of the renal arteries. 8. Untreated hypothyroid or hypo-parathyroid. 9. 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 10. Renal artery anatomy as assessed by imaging (CT-angiogram or, MR angiogram or renal angiogram) meeting the following criteria: 1. Single renal artery or two renal arteries, if either has a diameter of < 5 mm or > 7 mm or a length of < 11 mm, 2. Accessory renal arteries with diameter > 2.0 mm and < 5.0 mm, 3. Excessive renal artery tortuosity based on Investigator judgment, 4. Moderate or severe, and diffuse renal artery calcification, and/or 5. Renal anatomic renovascular abnormalities (as assessed by renal imaging) that would increase the risk of renal catheterization. 11. Occlusive peripheral vascular disease that would preclude percutaneous access for the procedure. 12. Patient is known to have a unilateral non-functioning kidney or unequal renal size (> 2cm difference in renal length between kidneys). 13. Single kidney, kidney tumor, urinary tract obstruction, or other anatomic abnormality. Note: Simple renal cysts are not an exclusion. 14. Previous renal denervation. 15. History of renal transplantation. 16. Estimated eGFR (by the CKD-Epi formula) =45 mL/min per 1.73 m2, or on chronic renal replacement therapy. Patients with eGFR of <60 mL/min per 1.73 m2 will undergo additional renal function monitoring post procedure and/or contrast exsposure. 17. Unexplained hypokalemia (i.e. K < 3.5 mEq/L in patients not on a potassium-wasting diuretic). 18. Patient in whom an ABPM device cannot be used due to arm size (>50 cm arm circumference) or other reasons as identified by the Investigator or study coordinator. 19. Patient with severe cardiac valve stenosis for which, in the opinion of the Investigator, a significant reduction of blood pressure is contraindicated. 20. Heart failure greater than asymptomatic, New York Heart Association Functional Classification, class I, stage B heart failure 21. Patient with history of myocardial infarction, unstable angina pectoris, or stroke during the 6 months prior to screening 22. Known primary or secondary pulmonary hypertension. 23. Active infection. 24. Patient requiring chronic oxygen support or has severe COPD. 25. Patient has known hypersensitivity to contrast agents that cannot be adequately pre-medicated 26. A known hypersensitivity to Dehydrated Alcohol Injection. 27. Platelet count < 75,000/microliter and/or known bleeding diathesis or coagulopathy at time of screening. 28. Receiving anticoagulant drugs (e.g., warfarin, dabigatran, rivaroxaban, apixaban, edoxaban, or low molecular weight heparins), that in the opinion of the investigator, would affect the safety of the trial procedure. Use of antiplatelet drugs such as aspirin and/or thienopyridines (e.g., clopidogrel) are permitted. 29. Patient has current problems with substance abuse (e.g. alcohol, illegal drugs, etc.). 30. Patient on high dose of steroids or immunosuppressant therapy. 31. Patient has a history of myocardial infarction, unstable angina pectoris, or stroke during the 3 months prior to screening. 32. Patients with a history of pre-eclampsia 33. patients with fibromuscular dysplasia 34. patients with history of pyelonephritis within 6 months 35. patients with history of recurrent (> one episode) kidney stones or history of kidney stones within the last year 36. Pregnant or nursing or planning to become pregnant during the trial time period. Note: If subject is of childbearing potential, as defined in the protocol, agrees to use of contraception. 37. Any acute or chronic condition that the investigator believes will adversely affect the ability to interpret the data or will prevent the subject from completing the trial procedures, or has a life expectancy of < 12 months. |
Country | Name | City | State |
---|---|---|---|
United States | The Institute for Exercise and Environmental Medicine | Dallas | Texas |
Lead Sponsor | Collaborator |
---|---|
University of Texas Southwestern Medical Center | National Institute of Neurological Disorders and Stroke (NINDS) |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Renal sympathetic activity | 18F-Fluorodopamine scanning of the kidney | Change in renal sympathetic activity at 8 weeks | |
Secondary | Blood pressure | 24-hour ambulatory blood pressure | Change in ambulatory blood pressure 24 hours, 1 week, 8 weeks, 6 months and 12 months after denervation. | |
Secondary | Muscle sympathetic activity | Muscle sympathetic nervous system activity at rest and during autonomic function testing | Change in Muscle sympathetic nervous system activity 8 weeks, 6 months after renal denervation | |
Secondary | Vascular function | Flow mediated dilation | Change in flow mediated dilation 8 weeks, 6 months after renal denervation | |
Secondary | Vascular stiffness | Pulse wave velocity | Change in pulswave velocity at 8 weeks, 6 months after renal denervation |
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