Transcutaneous Electrical Nerve Stimulation in Patients With Angina and Non-Obstructive Coronary Arteries (TENS-ANOCA)

The Novel Use of Transcutaneous Electrical Nerve Stimulation in Patients With Angina and Non-Obstructive Coronary Arteries: a Pilot Study

In patients with angina pectoris undergoing a coronary angiography (CAG) up to 40% do not have obstructive coronary artery disease (CAD). The majority of patients with no obstructive CAD are women with a frequency of up to 70% compared to 50% in men. These patients are diagnosed as having angina and non-obstructive coronary arteries (ANOCA). There are two endotypes of ANOCA. The first endotype is microvascular angina (MVA) caused by a combination of structural microcirculatory remodelling and functional arteriolar dysregulation, also called coronary microvascular dysfunction (CMD). The second endotype is vasospastic angina (VSA) caused by epicardial coronary artery spasm that occurs when a hyper-reactive epicardial coronary segment is exposed to a vasoconstrictor stimulus. Both endotypes of ANOCA are associated with significantly greater one-year risk of myocardial infarction (MI) and all-cause mortality, have a significantly impaired quality of life and have a high health care resource utilisation.

The current treatment for ANOCA consists of three aspects. The first aspect is managing lifestyle factors such as weight management, smoking cessation and exercise. The second aspect is managing known cardiovascular risk factors such as hypertension, dyslipidaemia and diabetes mellitus. And the third aspect is antianginal medication. In both endotypes ACE inhibitors or angiotensin II receptor blockers should be considered. In MVA the antianginal medication that can be used are betablocker, calcium channel blocker, nicorandil, ranolazine, ivabradine and/or trimetazidine. In VSA calcium channel blocker, long-acting nitrate and/or nicorandil can be initiated as antianginal therapy. Despite these treatment option approximately 25% of ANOCA patients have refractory angina symptoms.

A possible treatment modality for ANOCA patients with refractory angina pectoris is spinal cord stimulation (SCS) or transcutaneous electrical nerve stimulation (TENS). Previous research (in patients with cardiac syndrome X) has shown that SCS improves time until angina and ischaemia, significantly less angina and an improvement in quality of life. These findings suggest that SCS and/or TENS could be a possible treatment modality for patients with ANOCA.

The aim of this pilot study is to investigate whether treatment with TENS during a one month period leads to a significant reduction of angina pectoris and therefore a significant improvement in quality of life in patients with proven ANOCA, encompassing both endotypes (MVA and VSA).

Study Overview

• Status: Recruiting
• Conditions: Microvascular Angina; Vasospastic Angina
• Intervention / Treatment: Device: Transcutaneous Electrical Nerve Stimulation

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Inge Wijnbergen, MD, PhD; Phone Number: +31402397000; Email: inge.wijnbergen@catharinaziekenhuis.nl
• Study Contact Backup: Name: Fabienne Vervaat, MD; Phone Number: +31402397000; Email: fabienne.vervaat@catharinaziekenhuis.nl

Study Locations

• Netherlands
  • Noord Brabant
    • Eindhoven, Noord Brabant, Netherlands, 5623EJ
      • Recruiting
      • Catharina Hospital
      • Contact: Fabienne E Vervaat, MD; Phone Number: 0031402397000; Email: fabienne.vervaat@catharinaziekenhuis.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Angina and no obstructive coronary artery disease (ANOCA) (CCS class III or IV)

• Microvascular angina (MVA):

  • FFR > 0.8
  • CFR < 2.0
  • IMR ≥ 25

• Vasospastic angina (VSA):

  • FFR > 0.8
  • CFR ≥ 2.0
  • IMR < 25
  • During acetylcholine testing: ≥ 90% diameter reduction, angina pectoris and ischaemic ECG changes

• Persisting angina pectoris despite optimal medical therapy (OMT) defined as:

  • MVA: Betablocker, calcium channel blocker, nicorandil and/or ivabradine (Important side note: ranolazine and trimetazidine cannot be prescribed in the Netherlands).
  • VSA: Calcium channel blocker, long-acting nitrate and/or nicorandil. In the maximum tolerated dose. If the patient is currently not using one of the medications due to side-effects, this should be clearly stated.
• Age > 18 years

Exclusion Criteria:

• Both endotypes (VSA and MVA) present based on CFT findings.
• Inability to give informed consent
• Inability to perform a 6-minute walking test
• The presence of a cardiac implanted electronic device (CIED); pacemaker and/or Implantable Cardiac Defibrillator (ICD). Due to the risk of interference between TENS and CIED
• Presence of a spinal cord stimulator for another indication such as complex regional pain syndrome, failed back surgery syndrome, etc.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Open label; See intervention: all patients included in the study will receive TENS treatment for a period of 1 month	Device: Transcutaneous Electrical Nerve Stimulation; Device consists of two electrodes that are applied to the chest region and are connected to a battery operated TENS (Frequency 80Hz, pulse width 150us and amplitude variable (patient dependent)). The device will be used a minimum of three times daily for 30 minutes and additionally during symptoms.; Other Names: TENS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in summary score of Seattle Angina Questionnaire	Change in the summary score of the Seattle Angina Questionnaire (SS SAQ) after 1 month treatment with TENS, compared to baseline.	Baseline; 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in physical limitations domain of Seattle Angina Questionnaire	Change in physical limitations domain of the Seattle Angina Questionnaire (PL SAQ) after 1 month treatment with TENS, compared to baseline.	Baseline; 1 month
Change in angina frequency domain of Seattle Angina Questionnaire	Change in angina frequency domain of the Seattle Angina Questionnaire (AF SAQ) after 1 month treatment with TENS, compared to baseline.	Baseline; 1 month
Change in angina stability domain of Seattle Angina Questionnaire	Change in angina stability domain of the Seattle Angina Questionnaire (AS SAQ) after 1 month treatment with TENS, compared to baseline.	Baseline; 1 month
Change in treatment satisfaction domain of Seattle Angina Questionnaire	Change in treatment satisfaction domain of the Seattle Angina Questionnaire (TS SAQ) after 1 month treatment with TENS, compared to baseline.	Baseline; 1 month
Change in quality of life domain of Seattle Angina Questionnaire	Change in quality of life domain of the Seattle Angina Questionnaire (QoL SAQ) after 1 month treatment with TENS, compared to baseline.	Baseline; 1 month
Changes in patient condition	Change in patient condition using the 6-minute walking test after 1 month treatment with TENS, compared to baseline	Baseline; 1 month
Change in CCS class	Change in grading of angina pectoris using the Canadian Cardiovascular Society (CCS) class after 1 month treatment with TENS compared to baseline	Baseline; 1 month

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects of TENS use	Register all side effects (such as skin irritation, tenderness and/or TENS discomfort) experienced by the patient over the 1 month treatment period	1 month

Collaborators and Investigators

• Sponsor: Catharina Ziekenhuis Eindhoven

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2024
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: May 2, 2024
• First Submitted That Met QC Criteria: May 2, 2024
• First Posted (Actual): May 6, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pain; Neurologic Manifestations; Chest Pain; Angina, Unstable; Angina Pectoris; Angina Pectoris, Variant; Microvascular Angina
• Other Study ID Numbers: NL84910.100.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No