SCRATCH-HTN Study: Evaluating Autonomic Neuromodulation Using Trans-cutaneous Vagal Stimulation in Hypertensive Patients

NCT05179343 | Completed DMC

• 1 other identifier: 2358563
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot, sham-controlled, double blind, single-site device clinical trial designed to evaluate the safety, acceptability and efficacy of non-invasive autonomic neuromodulation in a cohort of 63 adult patients with uncontrolled high blood pressure.

Conditions

Uncontrolled Hypertension; High Blood Pressure

Outcome Measures

Primary Outcomes (1)

• Change in average daytime ambulatory Systolic Blood Pressure (SBP) from baseline to the end of treatment.

  Daytime SBP values will be obtained with 24hr ABPM

  from baseline to 3 months

Secondary Outcomes (13)

• Change in average daytime ambulatory SBP and Diastolic Blood Pressure (DBP) from baseline and 1 month.

  from baseline to 1 month

• Change in average daytime ambulatory DBP from baseline to the end of treatment.

  from baseline to 3 months

• Controlled BP at the end of treatment defined as mean daytime ambulatory SBP<135 mmHg and mean daytime ambulatory DBP<85 mmHg.

  from baseline to 3 months

• Change in average 24-hour ambulatory SBP and DBP from baseline to the end of treatment.

  from baseline to 3 months

• Change in average office SBP and DBP from baseline to 1 month, and from baseline to the end of treatment (3 months).

  baseline to 1 month and baseline to 3 months

Study Arms (2)

Active arm

EXPERIMENTAL

Participants in this arm will receive the active AffeX-CT device.

Device: Active AffeX-CT device

Sham arm

SHAM COMPARATOR

Participants in this arm will receive the sham (inactive) AffeX-CT device.

Device: Sham AffeX-CT device

Interventions

Active AffeX-CT device DEVICE

(Trans-cutaneous Autonomic Neurostimulation) tAN treatment will be administered using AffeX-CT device (a device based on a totally TENS unit). AffeX device comprises of a battery-operated control unit, two electrode pairs arranged on ear clips and connected to the control unit with electrical leads. The AffeX device generates an electrical signal that is used to stimulate the nerves that naturally control the output from the sympathetic nervous system.

Active arm

Sham AffeX-CT device DEVICE

Sham Totally TENS device. The device is identical to the active device used in the study, but its only purpose is to act as a placebo. The ear-clip electrodes have been modified so that the electric current is not transmitted to the participant.

Sham arm

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has given written informed consent.
• Participant has sufficient knowledge of the English language to be able understand the participant information sheet and trial materials including outcome assessments.
• Participant is aged ≥18 years and \<80 years at the time of screening visit.
• Participant is taking between 1 to 4 antihypertensive medications (inclusive) at time of screening and baseline (randomisation) visit and is willing to adhere to no change in medication during the trial until end of the trial visit (visit 5). (NB. Participant on only one antihypertensive medication should be taking that medication for at least six weeks prior to the screening visit).
• Participant has confirmed diagnosis of hypertension.
• Participant meets BP criteria:
• 24-hour ambulatory BP monitoring (ABPM) at either screening visit or baseline (randomisation) visit, with mean daytime SBP of ≥135 mmHg and \<170 mmHg and mean daytime DBP of ≥85 mm Hg and \<115 mmHg (N.B. By default, Ambulatory Blood Pressure Monitoring \[ABPM\] at screening visit will be used at baseline visit. However, if there has been an addition of new medication after participants screening visit, 24-hour ABPM must be repeated at baseline visit).
• Participant has one or more of the following associated conditions:
• Obesity: BMI \>30 or waist circumference \>94 cm (men) or \> 80cm (women). (NB. For participants of South-East Asian/Chinese/Japanese origin these cut-offs are \>90 cm (men) or \>80 cm (women)).
• Type 2 diabetes - controlled or sub-optimally controlled (HbA1c ≤8.5% or ≤69 mmol/mol) on diet and/ or medications except insulin.
• Heart rate (average) ≥70 bpm at screening or baseline (randomisation) visit (measurement taken after 5 minutes of rest in a seated position and when finger probe has been placed for a minimum of 30 seconds thereafter) or a heart rate (average) ≥60 bpm at screening or baseline (randomisation) visit if the patient is taking beta-blocker medication.
• HbA1c ≥42 mmol/mol or fasting blood glucose (if available) ≥5.6 mmo/L AND either low HDL cholesterol (≤1.03 mmol/L for men and ≤1.29 mmol/L for women) or high triglyceride (triglycerides ≥1.7 mmol/L)
• Both low HDL cholesterol (≤1.03 mmol/L for men and ≤1.29 mmol/L for women) AND high triglyceride (triglycerides ≥1.7 mmol/L)
• Diagnosed or known case of polycystic ovarian syndrome.
• Female participants of child-bearing potential (all those below 55 years except if they are surgically sterile, meaning they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy, or formally diagnosed by their doctors to be post-menopausal) must agree to use the acceptable methods of contraception from the time of consent until last follow up visit.

You may not qualify if:

• Participant is unable and unwilling to use the AffeX-CT device daily.
• Participant has a small tragus (ie. the size or shape of the tragus is such that it doesn't allow the application of the ear-clips of the AffeX-CT device for a sustained period of time).
• Participant has a piercing on the tragus of the ear.
• Participant is diagnosed with atrial fibrillation or other form of cardiac arrhythmia
• Participant is known to have chronic kidney disease (CKD) stage 3b or higher or had eGFR \<45 ml/min/1.73 m2 in last three months prior to baseline (randomisation) visit.
• Participant has type 1 diabetes mellitus.
• Participant has type 2 diabetes mellitus on Insulin or those on oral antidiabetic medications with poor glycaemic control defined as HbA1c above 8.5% (or \>69 mmol/mol).
• Participant has a history of falls or symptoms of orthostatic hypotension in the last 3 months prior to baseline (randomisation) visit.
• Participant is pregnant, nursing or planning to become pregnant within the next 6 months.
• Participant suffers from chronic pain and has taken anti-inflammatory drugs for two or more days per week over the last month prior to baseline (randomisation) visit.
• Participant has clinically significant or symptomatic hypertension-mediated target organ damage such as severe heart failure with NYHA 4, end stage renal damage, medically diagnosed/imaging proven stroke, symptomatic peripheral vascular disease, or severe retinopathy.
• Participant has a history of stable or unstable angina or had an acute coronary event within 3 months prior to baseline (randomisation) visit or had a myocardial infarction within the last six months of enrolment prior to baseline (randomisation) visit.
• Participant has a history of renal denervation within last 1 year prior to baseline (randomisation) visit.
• Participant has a therapeutic implantable electronic/electrical device such as pacemaker, implantable cardioverter-defibrillators (ICDs), implanted vagal stimulators.
• Participant has history of hospitalization (\> 24 hour) for heart failure, or cerebrovascular accidents, or history of stroke diagnosed based on imaging or evidence of specialist diagnosis or any other indirect evidence such as discharge summary or clinical letter (at any time in the past).

Sponsors & Collaborators

• Queen Mary University of London: lead
• Health Innovation Oxford and Thames Valley (Oxford AHSN): collaborator

Study Sites (1)

Barts Health NHS Trust

London, E1 1FR, United Kingdom

Location

Related Publications (24)

• Markle W, M. Fisher, and R. Smego. Understanding Global Health. Economics and Global Health. 2007.

  BACKGROUND

• Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, Clement DL, Coca A, de Simone G, Dominiczak A, Kahan T, Mahfoud F, Redon J, Ruilope L, Zanchetti A, Kerins M, Kjeldsen SE, Kreutz R, Laurent S, Lip GYH, McManus R, Narkiewicz K, Ruschitzka F, Schmieder RE, Shlyakhto E, Tsioufis C, Aboyans V, Desormais I; ESC Scientific Document Group. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018 Sep 1;39(33):3021-3104. doi: 10.1093/eurheartj/ehy339. No abstract available.

  PMID: 30165516 BACKGROUND

• England PH. Health matters: preventing cardiovascular disease 2019.

  BACKGROUND

• Foundation BH. BHF Coronavirus and Heart & Circulatory Disease Statistics. 2020.

  BACKGROUND

• Egan BM, Kjeldsen SE, Grassi G, Esler M, Mancia G. The global burden of hypertension exceeds 1.4 billion people: should a systolic blood pressure target below 130 become the universal standard? J Hypertens. 2019 Jun;37(6):1148-1153. doi: 10.1097/HJH.0000000000002021.

  PMID: 30624370 BACKGROUND

• England PH. Hypertension prevalence estimates in England. 2017;2020.

  BACKGROUND

• England PH. Tackling high blood pressure From evidence into action. 2014.

  BACKGROUND

• Achelrod D, Wenzel U, Frey S. Systematic review and meta-analysis of the prevalence of resistant hypertension in treated hypertensive populations. Am J Hypertens. 2015 Mar;28(3):355-61. doi: 10.1093/ajh/hpu151. Epub 2014 Aug 25.

  PMID: 25156625 BACKGROUND

• Abegaz TM, Shehab A, Gebreyohannes EA, Bhagavathula AS, Elnour AA. Nonadherence to antihypertensive drugs: A systematic review and meta-analysis. Medicine (Baltimore). 2017 Jan;96(4):e5641. doi: 10.1097/MD.0000000000005641.

  PMID: 28121920 BACKGROUND

• Carey RM, Calhoun DA, Bakris GL, Brook RD, Daugherty SL, Dennison-Himmelfarb CR, Egan BM, Flack JM, Gidding SS, Judd E, Lackland DT, Laffer CL, Newton-Cheh C, Smith SM, Taler SJ, Textor SC, Turan TN, White WB; American Heart Association Professional/Public Education and Publications Committee of the Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology; Council on Genomic and Precision Medicine; Council on Peripheral Vascular Disease; Council on Quality of Care and Outcomes Research; and Stroke Council. Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association. Hypertension. 2018 Nov;72(5):e53-e90. doi: 10.1161/HYP.0000000000000084.

  PMID: 30354828 BACKGROUND

• Dahal K, Khan M, Siddiqui N, Mina G, Katikaneni P, Modi K, Azrin M, Lee J. Renal Denervation in the Management of Hypertension: A Meta-Analysis of Sham-Controlled Trials. Cardiovasc Revasc Med. 2020 Apr;21(4):532-537. doi: 10.1016/j.carrev.2019.07.012. Epub 2019 Jul 26.

  PMID: 31420197 BACKGROUND

• Gupta A, Prince M, Bob-Manuel T, Jenkins JS. Renal denervation: Alternative treatment options for hypertension? Prog Cardiovasc Dis. 2020 Jan-Feb;63(1):51-57. doi: 10.1016/j.pcad.2019.12.007. Epub 2019 Dec 27.

  PMID: 31884099 BACKGROUND

• Azizi M, Schmieder RE, Mahfoud F, Weber MA, Daemen J, Lobo MD, Sharp ASP, Bloch MJ, Basile J, Wang Y, Saxena M, Lurz P, Rader F, Sayer J, Fisher NDL, Fouassier D, Barman NC, Reeve-Stoffer H, McClure C, Kirtane AJ; RADIANCE-HTN Investigators. Six-Month Results of Treatment-Blinded Medication Titration for Hypertension Control After Randomization to Endovascular Ultrasound Renal Denervation or a Sham Procedure in the RADIANCE-HTN SOLO Trial. Circulation. 2019 May 28;139(22):2542-2553. doi: 10.1161/CIRCULATIONAHA.119.040451. Epub 2019 Mar 17.

  PMID: 30880441 BACKGROUND

• Kandzari DE, Bohm M, Mahfoud F, Townsend RR, Weber MA, Pocock S, Tsioufis K, Tousoulis D, Choi JW, East C, Brar S, Cohen SA, Fahy M, Pilcher G, Kario K; SPYRAL HTN-ON MED Trial Investigators. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018 Jun 9;391(10137):2346-2355. doi: 10.1016/S0140-6736(18)30951-6. Epub 2018 May 23.

  PMID: 29803589 BACKGROUND

• Clancy JA, Mary DA, Witte KK, Greenwood JP, Deuchars SA, Deuchars J. Non-invasive vagus nerve stimulation in healthy humans reduces sympathetic nerve activity. Brain Stimul. 2014 Nov-Dec;7(6):871-7. doi: 10.1016/j.brs.2014.07.031. Epub 2014 Jul 16.

  PMID: 25164906 BACKGROUND

• Bretherton B, Atkinson L, Murray A, Clancy J, Deuchars S, Deuchars J. Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation. Aging (Albany NY). 2019 Jul 30;11(14):4836-4857. doi: 10.18632/aging.102074.

  PMID: 31358702 BACKGROUND

• Redgrave J, Day D, Leung H, Laud PJ, Ali A, Lindert R, Majid A. Safety and tolerability of Transcutaneous Vagus Nerve stimulation in humans; a systematic review. Brain Stimul. 2018 Nov-Dec;11(6):1225-1238. doi: 10.1016/j.brs.2018.08.010. Epub 2018 Aug 23.

  PMID: 30217648 BACKGROUND

• Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016 Mar 5;387(10022):957-967. doi: 10.1016/S0140-6736(15)01225-8. Epub 2015 Dec 24.

  PMID: 26724178 BACKGROUND

• van Bilsen M, Patel HC, Bauersachs J, Bohm M, Borggrefe M, Brutsaert D, Coats AJS, de Boer RA, de Keulenaer GW, Filippatos GS, Floras J, Grassi G, Jankowska EA, Kornet L, Lunde IG, Maack C, Mahfoud F, Pollesello P, Ponikowski P, Ruschitzka F, Sabbah HN, Schultz HD, Seferovic P, Slart RHJA, Taggart P, Tocchetti CG, Van Laake LW, Zannad F, Heymans S, Lyon AR. The autonomic nervous system as a therapeutic target in heart failure: a scientific position statement from the Translational Research Committee of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail. 2017 Nov;19(11):1361-1378. doi: 10.1002/ejhf.921. Epub 2017 Sep 26.

  PMID: 28949064 BACKGROUND

• Rahimi K. Blood pressure reduction - lower really is better. European Society of Cardiology. 2020.

  BACKGROUND

• Mueller ST, Piper BJ. The Psychology Experiment Building Language (PEBL) and PEBL Test Battery. J Neurosci Methods. 2014 Jan 30;222:250-9. doi: 10.1016/j.jneumeth.2013.10.024. Epub 2013 Nov 20.

  PMID: 24269254 BACKGROUND

• Voils CI, Maciejewski ML, Hoyle RH, Reeve BB, Gallagher P, Bryson CL, Yancy WS Jr. Initial validation of a self-report measure of the extent of and reasons for medication nonadherence. Med Care. 2012 Dec;50(12):1013-9. doi: 10.1097/MLR.0b013e318269e121.

  PMID: 22922431 BACKGROUND

• Bang H, Ni L, Davis CE. Assessment of blinding in clinical trials. Control Clin Trials. 2004 Apr;25(2):143-56. doi: 10.1016/j.cct.2003.10.016.

  PMID: 15020033 BACKGROUND

• Bastien CH, Vallieres A, Morin CM. Validation of the Insomnia Severity Index as an outcome measure for insomnia research. Sleep Med. 2001 Jul;2(4):297-307. doi: 10.1016/s1389-9457(00)00065-4.

  PMID: 11438246 BACKGROUND

MeSH Terms

Conditions

Hypertension

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Ajay K Gupta

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Eligible participants will be randomised at the baseline visit to either the active (tAN) or sham (sham-tAN) device arm of the trial at a ratio 2:1 ratio.

Study Record Dates

• First Submitted: December 16, 2021
• First Posted: January 5, 2022
• Study Start: August 1, 2022
• Primary Completion: September 8, 2025
• Study Completion: September 8, 2025
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)