Transcutaneous Auricular Vagus Nerve Stimulation in Upper Extremity Lymphedema

NCT06069908 | Completed DMC

• 1 other identifier: OzgeO
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 2

Brief Summary

Lymphedema is an inflammatory disease characterized by abnormal accumulation of excess water, plasma proteins, and extravascular blood and parenchymal cells in the affected upper and lower arms, chest and/or trunk due to inadequate lymphatic transport capacity, and is associated with high-severity, recurrent soft tissue infections that can lead to sepsis and even death. Although there is no definitive treatment for lymphedema, a Complex Decongestive Treatment approach that includes manual lymph drainage, skin care, special exercises, compression and personal care has been described to slow down the progression of the disease and prevent secondary complications. In addition, parasympathetic nerve activation has been described, similar to vagus nerve activation with manual lymphatic drainage. system activation can be increased. The aim of our study was to investigate the effect of transcutaneous auricular vagus nerve stimulation on quality of life, grip strength and manual dexterity in patients with unilateral upper extremity lymphedema. It was planned as a randomized controlled experimental study. The universe of the study will consist of lymphedema patients hospitalized in Gaziosmanpaşa Physical Therapy Rehabilitation Education and Research Hospital, and the sample will consist of 27 volunteer patients who meet the inclusion and exclusion criteria. The study was planned as a single-center (Gaziosmanpaşa Education and Research Hospital). Participants will be randomly divided into three groups. The groups will be determined by simple randomization method. Only Complex Decongestive Treatment (manual lymph drainage, skin care, special exercises, compression) approach will be applied to the first group, Complex Decongestive Treatment and sham transcutaneous vagus nerve stimulation will be applied to the second group, and transcutaneous vagus nerve stimulation will be applied in addition to Complex Decongestive Treatment to the third group. Data collected from the patients will be entered into SPSS 21.0 package program to create a data set and statistical analyses will be performed.

Conditions

Quality of Life; Lymphedema; Hand Grasp; Grip; Strength; Edema

Keywords

Lymphedema; Hand Grip; Grip Strength; Quality of Life

Outcome Measures

Primary Outcomes (1)

• Extremity circumference measurement as the primary outcome measure

  Upper Extremity Circumference Measurement will be evaluated for both upper extremities. Assuming the wrist pivot point, markings will be made every 4 cm up to the axilla. The difference between the affected and healthy sides will be determined by measuring the circumference with a tape measure at the marked points.

  It will be evaluated before starting and at the end of treatment. It will take 3 weeks.

Secondary Outcomes (3)

• Gross grip strength

  It will be evaluated before starting and at the end of treatment. It will take 3 weeks.

• Manual Dexterity

  It will be evaluated before starting and at the end of treatment. It will take 3 weeks.

• Life Quality

  It will be evaluated before starting and at the end of treatment. It will take 3 weeks.

Study Arms (3)

Complex Decongestive Treatment

PLACEBO COMPARATOR

Complex Decongestive Treatment (manual lymph drainage, skin care, special exercises, compression) approach. It will be applied 5 days a week for 3 weeks.

Other: Complex Decongestive Treatment; Other: Exercise

Sham transcutaneous vagus nerve stimulation

SHAM COMPARATOR

In sham transcutaneous vagus nerve stimulation application, the device electrode will be placed in the superior scapha region of the outer ear, where the vagus nerve has no innervation, and no current will be given.Complex Decongestive Therapy and sham transcutaneous vagus nerve stimulation.It will be applied 5 days a week for 3 weeks.

Other: Complex Decongestive Treatment; Other: Sham transcutaneous vagus nerve stimulation; Other: Exercise

Transcutaneous vagus nerve stimulation

ACTIVE COMPARATOR

Transcutaneous vagus nerve stimulation will be applied in addition to Complex Decongestive Therapy.It will be applied 5 days a week for 3 weeks.

Other: Complex Decongestive Treatment; Other: Transcutaneous Auricular Vagus Nerve Stimulation; Other: Exercise

Interventions

Complex Decongestive Treatment OTHER

Complex Decongestive Treatment (manual lymph drainage, skin care, special exercises, compression) approach. It will be applied 5 days a week for 3 weeks

Complex Decongestive Treatment; Sham transcutaneous vagus nerve stimulation; Transcutaneous vagus nerve stimulation

Sham transcutaneous vagus nerve stimulation OTHER

In sham transcutaneous vagus nerve stimulation application, the device electrode will be placed in the superior scapha region of the outer ear, where the vagus nerve has no innervation, and no current will be given.Complex Decongestive Therapy and sham transcutaneous vagus nerve stimulation.It will be applied 5 days a week for 3 weeks.

Sham transcutaneous vagus nerve stimulation

Transcutaneous Auricular Vagus Nerve Stimulation OTHER

Transcutaneous vagus nerve stimulation will be applied in addition to Complex Decongestive Therapy.It will be applied 5 days a week for 3 weeks.

Transcutaneous vagus nerve stimulation

Exercise OTHER

Patients will undergo lymphedema-specific exercises 5 days a week for 3 weeks.

Complex Decongestive Treatment; Sham transcutaneous vagus nerve stimulation; Transcutaneous vagus nerve stimulation

Eligibility Criteria

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

You may qualify if:

• Between the ages of 18-65
• Diagnosed with secondary lymphedema disease by the physician
• Minimum of three months after surgery
• Stage 2 and 3 patients
• Native speaker Turkish
• Individuals who agreed to participate in the study

You may not qualify if:

• Individuals with any neurological or orthopedic problems in the upper extremity
• Individuals undergoing upper extremity surgery
• Presence of cardiac edema
• Presence of arterial disease
• Presence of acute venous disease
• Those with sensory impairment
• Those with cardiac rhythm disorders
• Individuals with cooperation problems

Sponsors & Collaborators

• Seda Saka: lead

Study Sites (2)

Gaziosmanpaşa Training and Research Hospital

Istanbul, Gaziosmanpaşa, 34255, Turkey (Türkiye)

Location

Halic University

Istanbul, Turkey (Türkiye)

Location

Related Publications (9)

• Capilupi MJ, Kerath SM, Becker LB. Vagus Nerve Stimulation and the Cardiovascular System. Cold Spring Harb Perspect Med. 2020 Feb 3;10(2):a034173. doi: 10.1101/cshperspect.a034173.

  PMID: 31109966 BACKGROUND

• Cerritelli F, Frasch MG, Antonelli MC, Viglione C, Vecchi S, Chiera M, Manzotti A. A Review on the Vagus Nerve and Autonomic Nervous System During Fetal Development: Searching for Critical Windows. Front Neurosci. 2021 Sep 20;15:721605. doi: 10.3389/fnins.2021.721605. eCollection 2021.

  PMID: 34616274 BACKGROUND

• de Sire A, Losco L, Lippi L, Spadoni D, Kaciulyte J, Sert G, Ciamarra P, Marcasciano M, Cuomo R, Bolletta A, Invernizzi M, Cigna E. Surgical Treatment and Rehabilitation Strategies for Upper and Lower Extremity Lymphedema: A Comprehensive Review. Medicina (Kaunas). 2022 Jul 19;58(7):954. doi: 10.3390/medicina58070954.

  PMID: 35888673 BACKGROUND

• Drouin JS, Pfalzer L, Shim JM, Kim SJ. Comparisons between Manual Lymph Drainage, Abdominal Massage, and Electrical Stimulation on Functional Constipation Outcomes: A Randomized, Controlled Trial. Int J Environ Res Public Health. 2020 Jun 1;17(11):3924. doi: 10.3390/ijerph17113924.

  PMID: 32492920 BACKGROUND

• Farmer AD, Strzelczyk A, Finisguerra A, Gourine AV, Gharabaghi A, Hasan A, Burger AM, Jaramillo AM, Mertens A, Majid A, Verkuil B, Badran BW, Ventura-Bort C, Gaul C, Beste C, Warren CM, Quintana DS, Hammerer D, Freri E, Frangos E, Tobaldini E, Kaniusas E, Rosenow F, Capone F, Panetsos F, Ackland GL, Kaithwas G, O'Leary GH, Genheimer H, Jacobs HIL, Van Diest I, Schoenen J, Redgrave J, Fang J, Deuchars J, Szeles JC, Thayer JF, More K, Vonck K, Steenbergen L, Vianna LC, McTeague LM, Ludwig M, Veldhuizen MG, De Couck M, Casazza M, Keute M, Bikson M, Andreatta M, D'Agostini M, Weymar M, Betts M, Prigge M, Kaess M, Roden M, Thai M, Schuster NM, Montano N, Hansen N, Kroemer NB, Rong P, Fischer R, Howland RH, Sclocco R, Sellaro R, Garcia RG, Bauer S, Gancheva S, Stavrakis S, Kampusch S, Deuchars SA, Wehner S, Laborde S, Usichenko T, Polak T, Zaehle T, Borges U, Teckentrup V, Jandackova VK, Napadow V, Koenig J. International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020). Front Hum Neurosci. 2021 Mar 23;14:568051. doi: 10.3389/fnhum.2020.568051. eCollection 2020.

  PMID: 33854421 BACKGROUND

• Franchignoni F, Vercelli S, Giordano A, Sartorio F, Bravini E, Ferriero G. Minimal clinically important difference of the disabilities of the arm, shoulder and hand outcome measure (DASH) and its shortened version (QuickDASH). J Orthop Sports Phys Ther. 2014 Jan;44(1):30-9. doi: 10.2519/jospt.2014.4893. Epub 2013 Oct 30.

  PMID: 24175606 BACKGROUND

• Garcia Nores GD, Ly CL, Savetsky IL, Kataru RP, Ghanta S, Hespe GE, Rockson SG, Mehrara BJ. Regulatory T Cells Mediate Local Immunosuppression in Lymphedema. J Invest Dermatol. 2018 Feb;138(2):325-335. doi: 10.1016/j.jid.2017.09.011. Epub 2017 Sep 20.

  PMID: 28942366 BACKGROUND

• Hilz MJ. Transcutaneous vagus nerve stimulation - A brief introduction and overview. Auton Neurosci. 2022 Dec;243:103038. doi: 10.1016/j.autneu.2022.103038. Epub 2022 Sep 27.

  PMID: 36201901 BACKGROUND

• Ahmed U, Chang YC, Zafeiropoulos S, Nassrallah Z, Miller L, Zanos S. Strategies for precision vagus neuromodulation. Bioelectron Med. 2022 May 30;8(1):9. doi: 10.1186/s42234-022-00091-1.

  PMID: 35637543 RESULT

MeSH Terms

Conditions

Lymphedema; Edema

Interventions

Exercise

Condition Hierarchy (Ancestors)

Lymphatic Diseases; Hemic and Lymphatic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Kevser Gümüşsu, MD

  Gaziosmanpaşa Eğitim ve Araştırma Hastanesi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Masking Details: Participants will be randomly divided into three groups. Subjects will be instructed to draw an envelope from a secret box. Each envelope will contain a yellow, red and blue card and they will be assigned to one of the 3 groups of the study accordingly. Only the Complex Decongestive Treatment (manual lymph drainage, skin care, special exercises, compression) approach will be applied to the first group, Complex Decongestive Treatment and sham transcutaneous vagus nerve stimulation to the second group, and transcutaneous vagus nerve stimulation in addition to Complex Decongestive Treatment to the third group. The third party who has access to the box containing the envelopes will not be involved in the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor Doctor

Model Details: Demographic data related to the patient will be questioned with the Demographic Data and Anamnesis form prepared by the researchers. Circumference measurement was determined as the primary outcome measure, and gross grip strength, dexterity and quality of life were determined as the secondary outcome measures. To this end; Patients' upper extremity circumference was measured with a tape measure, gross grip strength was measured with Jamar Dynanometer, manual dexterity was measured with 9-Hole Peg Test, upper extremity problems were measured with Arm, Shoulder and Hand Problems Quick Questionnaire (Quick DASH), items related to people's quality of life and specific arm symptoms were measured. Lymphedema Functionality will be evaluated with the Disability and Health Survey (LFÖSA) and quality of life will be evaluated with the Quality of Life Questionnaire in Upper Extremity Lymphedema Patients (ULL-27).

Study Record Dates

• First Submitted: September 8, 2023
• First Posted: October 6, 2023
• Study Start: September 11, 2023
• Primary Completion: September 11, 2024
• Study Completion: December 11, 2024
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

TU (2)