The aim of this post-CE study is to collect data on the effects of renal sympathetic denervation on the insulin resistance and muscle sympathetic nerve activity (MSNA) in patients with metabolic syndrome and associated hypertension.
ID
Source
Brief title
Condition
- Other condition
- Vascular hypertensive disorders
Synonym
Health condition
Metabool Syndroom
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To determine the effects of renal sympathetic denervation on the insulin
resistance and muscle sympathetic nerve activity (MSNA) in patients with
metabolic syndrome and associated uncontrolled hypertension at 3 months after
renal denervation.
Secondary outcome
To determine the effects of renal sympathetic denervation on the insulin
resistance, MSNA and blood pressure long-term (12 months after renal
denervation).
Background summary
Metabolic syndrome is considered present when at least three of the following
five-component criteria are met:
1) systolic blood pressure *130 mmHg or diastolic blood pressure *85 mmHg or on
antihypertensive drug treatment in a patient with a history of hypertension;
2) fasting glucose *100 mg/dL (*5.6 mmol/L) or on drug treatment for elevated
glucose;
3) waist circumference *102 cm (*40 inches) for male or *88 cm (*35 inches) for
female;
4) triglycerides *150 mg/dL (*1.7 mmol/L) or on drug treatment for elevated
triglycerides;
5) high density lipid cholesterol (HDL-C) <40 mg/dL (<1.03 mmol/L) for male or
<50 mg/dL (<1.3 mmol/L) for female or on drug treatment for reduced HDL-C.
Each of these metabolic syndrome components is known to be an independent risk
factor of
cardiovascular morbidity and mortality with hypertension known to be one of the
highest
predictors. The occurrence of three or more of these components in individuals
with metabolic syndrome further increases the already elevated cardiovascular
risk. Hypertension is a very common component in individuals with metabolic
syndrome. The risk of cardiovascular and allcause mortality is almost doubled,
and the risk of developing type II diabetes mellitus also increases
approximately threefold if the metabolic syndrome is present.
Metabolic syndrome is also characterized by elevated sympathetic nerve activity
at fasting state and by insulin resistance with impaired sympathetic neural
response to the physiologic
hyperinsulinemia and oral glucose. This plays a role in the progression of
metabolic syndrome and the corresponding cardiovascular risks with direct and
indirect influences to the development and progression of organ damages.
Strategies to target specifically the elevated sympathetic nerve activity may
provide substantial clinical benefits to
patients with metabolic syndrome and associated hypertension.
The sympathetic innervation of the kidney is implicated in the pathogenesis of
hypertension
through enhanced renin secretion, sodium re-absorption and reduced blood flow.
Renal
sympathetic afferent and efferent nerves run within and adjacent to the wall of
the renal
arteries. In various experimental models, which include obesity-induced
hypertension,
the magnitude of hypertension has been reduced during the observation period
post renal sympathetic denervation. The percutaneous, catheter-based method
that delivers radiofrequency (RF) to the renal sympathetic nerves for the
ablation-induced renal sympathetic denervation has also been shown to result in
safe and effective lowering of blood pressure, lowering of MSNA, and possible
improvement of glucose metabolism in patients with resistant hypertension.
While sympathetic neural inhibition through renal sympathetic denervation may
provide
protection in patients with metabolic disorders and resistant hypertension at
high cardiovascular risk, the underlying mechanisms of metabolic and blood
pressure controls through renal sympathetic denervation remain uncertain.
Investigating the effect of renal denervation on the insulin resistance and
sympathetic nerve activity in this patient population may give us more insights
on the underlying mechanisms.
Study objective
The aim of this post-CE study is to collect data on the effects of renal
sympathetic denervation on the insulin resistance and muscle sympathetic nerve
activity (MSNA) in patients with metabolic syndrome and associated
hypertension.
Study design
This is a prospective, randomized, controlled, multi-center clinical
investigation of the EnligHTN* Renal Denervation System. Approximately 60
subjects will be enrolled with 2 to 3 study centers participating in the
clinical investigation. Subjects are randomized (3:1 ratio) to either Treatment
Group or Control Group and will be followed up for 1 year post procedure.
Intervention
The procedure consists of an ablation of the renal sympathetic nerves within
the renal arteries, by delivering RF energy via a percutaneous catheter. This
minimal invasive local method has a short procedure time, short hospitalization
and short recovery time.
Study burden and risks
The standard 75g OGTT is associated with minimal risks. The known, but rare,
adverse reactions include nausea, vomiting, abdominal bloating, headache and
hypoglycaemia.
Drawing blood may cause some discomfort or bruising. The blood vessel may
swell, blood may clot in the blood vessel, or the spot from which blood is
taken could become inflamed. In rare instances, there could be a minor
infection or bleeding. If this happens, it can easily be treated.
In the Nerve Activity Test, when the needle is locating the nerve for proper
nerve activity recording, it may cause momentary discomfort or pain.
The renal denervation is an interventional approach and as such carries some
potential risks which may include but are not limited to the following:
* Acute renal injury (renal infarction, renal hematoma)
* Access site complications (bleeding, arteriovenous fistula, access site
thrombosis, embolisation, pseudo-aneurysm, hematoma, limb ischemia, femoral
nerve injury or seroma)
* Allergic reaction against contrast media
* Bradycardia
* Collateral tissue injury
* Death
* Decompensated heart failure
* Disseminated intravascular coagulation
* Drug reactions
* Malignant or accelerated hypertension
* Renal vascular injury (renal artery dissection, renal artery thrombosis,
renal artery stenosis)
* Symptomatic hypotension
* Infection (access site infection or systemic infection)
* Myocardial infarction
* Neurologic event (acute ischemic or hemorrhagic brain injury)
* Pain, including back pain
* Renal failure
* Respiratory compromise
* Vasospasms
* Vasovagal episodes
When a renal artery angiogram is taken, the patient will be exposed to a small
amount of radiation. As part of everyday living, everyone is exposed to
naturally occurring background radiation and receives a dose of about 2
millisieverts (mSv) each year. The effective dose from this study is about 25
mSv, which is comparable to that received from several computed tomography
x-rays (CT) and nuclear medicine procedures.
The benefits from the research study should be weighed against the possible
detrimental effects of radiation, which includes an increased risk of fatal
cancer. In this particular study, the risk is moderate, and the estimated risk
of such harm is about 1 in 800. For comparison, this risk is about 200 times
lower than the cancer mortality rate in the general population of about one
case in every four people.
The effects of renal denervation on the unborn child and on the newborn baby
are not known. Because of this, it is important that study participants are not
pregnant or breast-feeding and do not become pregnant during the course of the
research study.
There may be other risks that are not known at this time.
Standaardruiter 13
VEENENDAAL 3905 PT
NL
Standaardruiter 13
VEENENDAAL 3905 PT
NL
Listed location countries
Age
Inclusion criteria
- Patient with office blood pressure *140/90 mmHg and 24-hour ambulatory blood pressure *130/80 mmHg at Enrollment despite treatment with two drugs at maximum tolerated doses
- Patient with a fasting glucose *100 mg/dL (*5.6 mmol/L) at Enrollment
- Patient with a waist circumference *102 cm (*40 inches) for male or *88 cm (*35 inches) for female at Enrollment
- Patient with any of the other metabolic syndrome diagnostic criteria listed as follows at Enrollment:
o Triglycerides *150 mg/dL (*1.7 mmol/L) or on drug treatment for elevated triglycerides
o High density lipid cholesterol (HDL-C) <40 mg/dL (<1.03 mmol/L) for male or <50 mg/dL
(<1.30 mmol/L) for female or on drug treatment for reduced HDL-C
- Patient is *18 and *80 years old
- Patient must be able and willing to provide written informed consent to participate in this clinical investigation
- Patient must be able and willing to comply with the required follow-up schedule
Exclusion criteria
* Patient with resistant hypertension or secondary hypertension
* Patient with type I diabetes mellitus or type II diabetes mellitus requiring insulin therapy
* Patient with prior renal angioplasty, renal denervation, indwelling renal stents and/or
aortic stent grafts
* Patient with renal arteries <4.0 mm in diameter
* Patient with significant renovascular abnormalities (such as renal artery stenosis >30%)
* Patient with an estimated glomerular filtration rate (eGFR) of <45 mL/min per 1.73 m2
using the Modified Diet in Renal Disease (MDRD) formula
* Patient with hemodynamically significant valvular heart disease, as determined by Study
Investigator
* Patient has had a myocardial infarction, unstable angina pectoris or cerebrovascular
accident less than 180 days at Enrollment or is expected to have cardiovascular
intervention within the next 180 days
* Patient is in chronic atrial fibrillation/flutter or with severe conduction abnormalities or
with an implantable cardioverter defibrillator (ICD) or pacemaker whose settings cannot
allow for radiofrequency (RF) energy delivery
* Patient is currently being treated with drugs that cause salt retention (such as systemic
corticosteroids or fludrocortisone)
* Patient with an active systemic infection or blood-clotting abnormalities
* Patient is pregnant or of childbearing potential and is not using adequate contraceptive
methods or nursing
* Patient is participating in another clinical investigation
* Patient has a life expectancy less than 12 months, as determined by Study Investigator
* Patient has an allergy for contrast agent used for the angiogram
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01911078 |
| CCMO | NL46078.041.13 |