To determine the effects of renal sympathetic denervation on insulin resistance and muscle sympathetic nerve activity (MSNA) in patients with metabolic syndrome at 3 months after renal denervation.
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 insulin resistance
and muscle sympathetic nerve activity (MSNA) in patients with metabolic
syndrome at 3 months after renal denervation.
Secondary outcome
To determine the effects of renal sympathetic denervation on insulin resistance
and MSNA longterm (12 months after renal denervation) for potential
confirmation of the primary observation at 3 months.
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 ablationinduced 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 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
To determine the effects of renal sympathetic denervation on insulin resistance
and muscle sympathetic nerve activity (MSNA) in patients with metabolic
syndrome at 3 months after renal denervation.
Study design
This is a prospective, randomized, controlled, blinded, multi-center
feasibility clinical investigation.
60 patients will be included in 2 or 3 different study centers. Patients will
be randomized (3:1ratio) to the renal denervation groep or control group en
will be followed for 12 months post procedure
MSNA measurement will be performed by a blinded investigator. Blinded means
that he.she is not informed about the randomization result of the patient.
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 7
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 Baseline despite the stable use of at least two anti-hypertensive drugs at maximum tolerated doses of the patient for at least 4 weeks
- Patient with a fasting glucose *100 mg/dL (*5.6 mmol/L) at Baseline or on drug treatment for elevated glucose
- Patient with a waist circumference *102 cm (*40 inches) for male or *88 cm (*35 inches) for female at Baseline
- Patient with any of the remaining two metabolic syndrome diagnostic criteria listed as follows at Baseline:
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 *70 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 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 Baseline 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), centrally acting sympatholytic antihypertensive drugs, direct vasodilators (such as alpha blockers) an continious positive airway pressure (CPAP) therapy for obstuctive sleep apnea.
- Patient with an active systemic infection or blood-clotting abnormalities or allergy to radiographic contrast
- 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
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 | NL50001.041.14 |