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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05179343
Other study ID # 2358563
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date August 1, 2022
Est. completion date December 31, 2025

Study information

Verified date April 2024
Source Queen Mary University of London
Contact Ajay K Gupta
Phone 020 7882 2858
Email ajay.gupta@qmul.ac.uk
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

SCRATCH-HTN trial is a randomised sham-controlled study designed to evaluate the safety, acceptability, and efficacy of trans-cutaneous autonomic neurostimulation (tAN) in a cohort of uncontrolled medicated hypertensive patients. SCRATCH-HTN trial is designed to test the hypothesis that tAN treatment is safe and acceptable to the patient, improves the control of blood pressure in hypertension and sense of well-being amongst those who are receiving the active treatment as compared to those on sham treatment. The study will recruit 63 patients with systemic arterial hypertension (male and female aged ≥18 years) who are receiving between one and three oral antihypertensive medications and remain hypertensive with blood pressure (BP) above target levels detailed below in the eligibility criteria. The participants will be randomly allocated to the active (tAN) or sham (sham-tAN) arms of the trial on 2:1 basis, respectively. The total treatment duration is 12 weeks. Self-administration of 30 min of tAN or sham stimulations once per day for the first two weeks, and then once every week for the rest of the trial period.


Recruitment information / eligibility

Status Recruiting
Enrollment 63
Est. completion date December 31, 2025
Est. primary completion date August 31, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 79 Years
Eligibility Inclusion Criteria: 1. Participant has given written informed consent. 2. Participant has sufficient knowledge of the English language to be able understand the participant information sheet and trial materials including outcome assessments. 3. Participant is aged =18 years and <80 years at the time of screening visit. 4. 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). 5. Participant has confirmed diagnosis of hypertension. 6. 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). 7. Participant has one or more of the following associated conditions: 1. 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)). 2. Type 2 diabetes - controlled or sub-optimally controlled (HbA1c =8.5% or =69 mmol/mol) on diet and/ or medications except insulin. 3. 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. 4. 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) 5. 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) 6. Diagnosed or known case of polycystic ovarian syndrome. 8. 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. 9. Participant is able to communicate satisfactorily with the Investigator and Investigation Site staff, and to participate in, and comply with all clinical study requirements. 10. Participants agrees to have all trial procedures performed and is able and willing to comply with all trial visits and protocol requirements. Exclusion Criteria: 1. Participant is unable and unwilling to use the AffeX-CT device daily. 2. 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). 3. Participant has a piercing on the tragus of the ear. 4. Participant is diagnosed with atrial fibrillation or other form of cardiac arrhythmia 5. 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. 6. Participant has type 1 diabetes mellitus. 7. 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). 8. Participant has a history of falls or symptoms of orthostatic hypotension in the last 3 months prior to baseline (randomisation) visit. 9. Participant is pregnant, nursing or planning to become pregnant within the next 6 months. 10. 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. 11. 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. 12. 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. 13. Participant has a history of renal denervation within last 1 year prior to baseline (randomisation) visit. 14. Participant has a therapeutic implantable electronic/electrical device such as pacemaker, implantable cardioverter-defibrillators (ICDs), implanted vagal stimulators. 15. 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). 16. Participant has mean daytime ABPM pulse pressure = 80 mmHg at screening or baseline (randomisation) visit. 17. Participant has a heart rate <50 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). 18. Participant has auricular dermatitis. 19. Participant has postural hypotension, defined as a fall > 20mmHg in SBP on standing at 3 minutes (compared with sitting). 20. Participant has a history of hospitalization for hypertensive emergency or urgency in the last six months of enrolment prior to baseline (randomisation) visit. 21. Participant is identified as unsuitable to participate by the CI/Co-Investigator(s) and/or Investigation site team for another reason (e.g., for other medical reasons, laboratory abnormalities, limited life expectancy, etc.). 22. Participants with history of epilepsy and are currently on anti-epileptic medication or those who are not on any anti-epileptic medication but have history of a seizure within last 10 years.

Study Design


Intervention

Device:
Active AffeX-CT 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.
Sham AffeX-CT 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.

Locations

Country Name City State
United Kingdom Barts Health NHS Trust London

Sponsors (2)

Lead Sponsor Collaborator
Queen Mary University of London Health Innovation Oxford and Thames Valley (Oxford AHSN)

Country where clinical trial is conducted

United Kingdom, 

References & Publications (24)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

England PH. Health matters: preventing cardiovascular disease 2019.

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

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

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. — View Citation

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

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. — View Citation

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. — View Citation

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

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Eur Heart J. 2019 Feb 1;40(5):475. — View Citation

* Note: There are 24 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Change in average daytime ambulatory SBP and Diastolic Blood Pressure (DBP) from baseline and 1 month. Daytime ambulatory SBP values will be obtained with 24hr ABPM from baseline to 1 month
Secondary Change in average daytime ambulatory DBP from baseline to the end of treatment. Daytime ambulatory DBP values will be obtained with 24hr ABPM from baseline to 3 months
Secondary Controlled BP at the end of treatment defined as mean daytime ambulatory SBP<135 mmHg and mean daytime ambulatory DBP<85 mmHg. Daytime ambulatory SBP and DBP will be obtained with 24hr ABPM from baseline to 3 months
Secondary Change in average 24-hour ambulatory SBP and DBP from baseline to the end of treatment. Daytime ambulatory SBP and DBP will be obtained with 24hr ABPM from baseline to 3 months
Secondary Change in average office SBP and DBP from baseline to 1 month, and from baseline to the end of treatment (3 months). Daytime ambulatory SBP and DBP will be obtained with a vital signs monitor baseline to 1 month and baseline to 3 months
Secondary Change in average daytime ambulatory HR, and in average night-time ambulatory HR from baseline to the end of treatment. Daytime and nigh-time ambulatory HR will be obtained with 24hr ABPM from baseline to 3 months
Secondary Change in BP variability defined as the coefficient of variation (SD/mean) of 24-hour ambulatory SBP, and of within-visit office SBP from baseline to the end of treatment. 24hr ambulatory SBP will be obtained with 24hr ABPM from baseline to 3 months
Secondary Change in Heart Rate (HR) variability defined as the coefficient of variation (SD/mean) of 24-hour ambulatory HR, and of within-visit office HR from baseline to the end of treatment. 24hr ambulatory HR will be obtained with 24hr ABPM from baseline to 3 months
Secondary Occurrence of a serious adverse event (SAE), fatal or non-fatal, within 3 months. SAEs will be collected through patient interviews, reporting and monitoring from baseline to 3 months
Secondary The occurrence of a major cardiovascular event (MACE), including myocardial infarction (MI), stroke, and cardiovascular-related mortality within 3 months. MACE will be collected through patient interviews, reporting and monitoring from baseline to 3 months
Secondary Change in Quality of life between baseline and the end of the treatment (3 months) using the EuroQol Visual Analogue score (0-100), and the EuroQol 5 Dimension (EQ5D) quality of life (QoL) questions. EQ-5D-5L questionnaire from baseline to 3 months
Secondary Change in sleep quality between baseline and the end of the treatment using the Insomnia Severity Index (ISI), a 7-item questionnaire with each question allowing responses on a 5-point Likert scale from 0-4. Responses summed to give an overall score of 0 ISI questionnaires from baseline to 3 months
Secondary Adherence to trial therapy, assessed as the proportion of days out of total days in follow-up when therapy was self-administered, and the average daily duration of self-administered therapy over the 3 months of follow-up (90 days). Study log-book from baseline to 3 months
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