Transcutaneous Electrical Nerve Stimulation (TENS) on Arterial Stiffness and Blood Pressure

NCT ID: NCT02365974

Last Updated: 2021-02-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-01
• Study Completion Date: 2022-06-30

Brief Summary

Uncontrolled blood pressure represents the main factor in the development of target organ lesions and, consequently, cardiovascular events, which are the leading cause of morbidity and mortality worldwide. In most cases resistant hypertension is preceded by target organ lesions, and is strongly influenced by risk factors or associated diseases. To control this disease requires an adequate and intense therapeutic approach that includes lifestyle changes and the use of several antihypertensive drugs. However, the results are not always satisfactory despite intensive treatment. Of the different pathophysiological mechanisms involved in the pathogenesis of resistant hypertension (RH), two, sympathetic overstimulation and therapies that block the sympathetic system, have been widely studied. But, these approaches are invasive and expensive. Another possible approach is by transcutaneous electrical nerve stimulation (TENS), a non-invasive method that modulates activity by inhibiting primary afferent pathways using low-frequency transcutaneous electrical stimulation. Some studies have shown that TENS reduces blood pressure in patients with hypertension. The current study will evaluate the effect of applying TENS in the cervicothoracic region of subjects with resistant hypertension, seeking to develop a new low cost and readily available therapy to treat this group of hypertensive individuals.

Detailed Description

Patients will be divided into two groups: treatment and control (sham group). The sham group will be submitted to the procedure to fit the stimulation equipment. However, these patients will not be submitted to stimulation. Both groups will undergo a physical examination at the start and end of the study period to determine anthropometric variables. The BMI, defined as the weight (kg) divided by the patient's height squared (m2), will be calculated. The height will be determined in centimeters using a measuring tape with the individual barefoot. Individuals with BMI <25 kg/m² will be classified as normal, overweight as a BMI between 25 and 30 kg/m², and obese as a BMI ≥30 kg/m². The waist circumference will be measured using a measuring tape at half the distance between the iliac crest and the lower costal margin. Patients will undergo the following tests before and after the end of the four-week study period: 24-hour ambulatory blood pressure monitoring (ABPM), 24-hour dynamic electrocardiography, continuous measurement of beat-to-beat BP, endothelial function measurement and radial artery applanation tonometry (AT).

Biochemical tests will be performed at two time points, before and after the four-week study period and include blood sugar, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), creatinine, potassium, uric acid, and plasma insulin levels. Blood sugar, TC, HDL-C and TG levels will be determined by colorimetry after fasting for 12 hours using a dimension device with the Dade Behring reagent. Diagnosis of diabetes mellitus (DM) will be established by patient history, the use of hypoglycemic drugs and measurement of the serum glucose. The LDL-C fraction will be calculated using the formula LDL-C = TC - HDL-C - TG / 5 (for TG <400 mg/dL). Additionally, the electrochemiluminescence method will be used to measure plasma insulin (immunoassay for the in vitro quantitative determination of human insulin in serum and plasma using the Elecsys 1010/2010 immunoassay and E170 modular analytics analyzers by Roche). The homeostasis model assessment of insulin resistance (HOMA-IR) index will be applied after obtaining blood sugar and insulin levels in order to determine insulin resistance and the functional capability of the pancreatic beta cells. Insulin resistance will be characterized when this ratio exceeds 2.71. The HOMA-IR index is calculated using the following formula:

HOMA-IR: Fasting insulin (McU/mL) x fasting glucose (mmol/L*) 22.5

In order to convert the glucose concentration to mmol/L it is necessary to multiply the value in mg/dL by 0.0555. Measurement of serum creatinine will be performed by a standardized enzyme-kinetic biochemical test and will be considered high when serum creatinine >1.4 mg/dL. Urinary sodium and potassium levels (mEq/L) will be evaluated by flame photometry. Urinary sodium excretion will be calculated by multiplying the urinary sodium and potassium concentrations in mEq/L by the 24-hour urine volume. The 24-hour urine volume and urinary creatinine concentrations will be assessed to calculate creatinine clearance adjusted for body surface.

Specific biochemical tests will be considered: serum aldosterone (AS), plasma renin activity (PRA), high-sensitivity C-reactive protein (hsCRP), metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinases (TIMP-1 and TIMP-2), nitrites and nitrates, interleukin-1, 6, 8, 10 and 18 (IL-1, IL-6, IL-8, IL-10 and IL-18), tumor necrosis factor (TNF-α), thromboxane B2 (TXB2), fibrinogen, intercellular adhesion molecule (ICAM-1), plasminogen activator inhibitor (PAI-1), angiotensin converting enzyme (ACE) and angiotensin II (Ang II).

Conditions

Hypertension; Vascular Stiffness; Autonomic Nervous System Diseases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Transcutaneous Electrical Stimulation

TENS will be applied in the cervicothoracic ganglion region located between the C7 and T4 vertebral processes for 40 minutes three times weekly for a total of four weeks. The intensity in milliamps (mA) will be adjusted depending on the sensitivity of each individual patient. The arrangement thereof will be parallel on each side of the C7 (channel 1) and T4 (channel 2) vertebral spinous processes.

Group Type: ACTIVE_COMPARATOR

Transcutaneous Electrical Stimulation

Intervention Type: DEVICE

TENS will be applied in the cervicothoracic ganglion region located between the C7 and T4 vertebral processes for 40 minutes three times weekly for a total of four weeks. The intensity in milliamps will be adjusted depending on the sensitivity of each individual patient.

No Transcutaneous Electrical Stimulation

The sham group will be submitted to the procedure to fit the stimulation equipment without be submitted to stimulation.

Group Type: SHAM_COMPARATOR

No Transcutaneous Electrical Stimulation

Intervention Type: DEVICE

The sham group will be submitted to the procedure to fit the stimulation equipment. without be submitted to stimulation.

Interventions

Transcutaneous Electrical Stimulation

TENS will be applied in the cervicothoracic ganglion region located between the C7 and T4 vertebral processes for 40 minutes three times weekly for a total of four weeks. The intensity in milliamps will be adjusted depending on the sensitivity of each individual patient.

Intervention Type: DEVICE

No Transcutaneous Electrical Stimulation

The sham group will be submitted to the procedure to fit the stimulation equipment. without be submitted to stimulation.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• RH patients taking at least three antihypertensive drugs at full doses, one of which is preferably a thiazide diuretic; Age between 40 and 70 years.

Exclusion Criteria

• Use of a cardiac pacemaker
• Cardiac electrical conduction abnormalities evidenced by ECG or stress test (ergometry)
• Dermatological abnormalities at the site of the application of TENS
• Uncontrolled diabetes patients using oral hypoglycemic agents or insulin with glycated Hb ≥ 7.5%
• Secondary Hypertension
• Patients who do not adhere to the lifestyle changes recommended by their physician such as low-sodium diet and weight loss
• Moderate to severe cervical-thoracic scoliosis
• Obesity with body mass index (BMI) ≥35 kg/m2

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital de Base

OTHER

Sponsor Role: lead

Responsible Party

JOSE FERNANDO VILELA-MARTIN

Coordinator of Hypertension Clinic

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

José F Vilela-Martin, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Fundação Faculdade Regional de Medicina de São José do Rio Preto

Central Contacts

José F Vilela-Martin, MD PhD

Role: CONTACT

vilelamartin@uol.com.br

551732015727 ext. 17

Luiz Tadeu Giollo Júnior, PT

Role: CONTACT

ltgg@hotmail.com

5517981326219

References

da Silva ML, Chiappa GR, da Silva VM, Neves LM, de Lima AC, Tomasi FP, Junior LT, Vilela-Martin JF, Bottaro M, Junior GC. Effect of transcutaneous electrical nerve stimulation on peripheral to central blood pressure ratio in healthy subjects. Clin Physiol Funct Imaging. 2016 Jul;36(4):293-7. doi: 10.1111/cpf.12227. Epub 2015 Jan 30.

Reference Type: BACKGROUND

PMID: 25640037 (View on PubMed)

Cipriano G Jr, Neder JA, Umpierre D, Arena R, Vieira PJ, Chiappa AM, Ribeiro JP, Chiappa GR. Sympathetic ganglion transcutaneous electrical nerve stimulation after coronary artery bypass graft surgery improves femoral blood flow and exercise tolerance. J Appl Physiol (1985). 2014 Sep 15;117(6):633-8. doi: 10.1152/japplphysiol.00993.2013. Epub 2014 Aug 7.

Reference Type: BACKGROUND

PMID: 25103974 (View on PubMed)

Vilela-Martin JF, Giollo-Junior LT, Chiappa GR, Cipriano-Junior G, Vieira PJ, dos Santos Ricardi F, Paz-Landim MI, de Andrade DO, Cestario Edo E, Cosenso-Martin LN, Yugar-Toledo JC, Cipullo JP. Effects of transcutaneous electrical nerve stimulation (TENS) on arterial stiffness and blood pressure in resistant hypertensive individuals: study protocol for a randomized controlled trial. Trials. 2016 Mar 29;17:168. doi: 10.1186/s13063-016-1302-8.

Reference Type: DERIVED

PMID: 27026087 (View on PubMed)

Other Identifiers

RH-07606212500005415

Identifier Type: -

Identifier Source: org_study_id