Lymphatic Function in Patients With Fontan Circulation: Effect of Physical Training

NCT05934578 | Completed DMC

• 1 other identifier: CAAE 61404222.6.0000.0068
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The Fontan operation has been used to treat complex cardiac anomalies with a single-functioning ventricle. A study performed by Instituto do Coracão-Hospital das Clínicas-Universidade de Sao Paulo (InCor/HCFMUSP)-Brazil, Hospital das Clínicas of Ribeirão Preto-Brazil, department of the University of Aarhus, and Rigshospitalet, Denmark demonstrated an impairment peripheral lymphatic function in Fontan patients compared with healthy controls. However, the ability to increase the frequency of contractions is impaired when stressed by hyperthermia. Lymph vessels in Fontan patients were unable to respond usually. The participants were only able to increase the frequency of contraction twice during stress, compared to a five-fold increase among healthy controls. At the microcirculation level, Fontan patients filtered less fluid into the capillaries interstitial space than healthy controls at venous occlusion pressure. Studies carried out at InCor/HCFMUSP demonstrated that supervised aerobic exercise training improves the functional capacity and neurovascular control in Fontan patients compared to the non-training control group. However, the effect of aerobic exercise and light muscle resistance performed through online rehabilitation has not yet been demonstrated in peripheral lymphatic function and microcirculation. Aim: Evaluate the effects of an aerobic and light muscle resistance exercise program on peripheral lymphatic function, capillary filtration, functional capacity, and quality of life in adults with Fontan circulation. Methods: The function of the superficial lymphatic vessels in the lower leg will be investigated during rest in supine and standing positions, using near-infrared fluorescence imaging using Indocyanine Green (ICG; Verdye, Diagnostic Green GmbH, Germany). The variables analyzed are contraction frequency (contraction/minute), pumping Pressure (mmHg), and packet velocity. Venous congestion plethysmography will perform to analyze the capillary filtration and cardiopulmonary exercise test for functional capacity. The quality of life will be evaluated using the SF-36 Short-Form questionnaire. Expected results: the physical training improves peripheral lymphatic function, capillary filtration, functional capacity, and quality of life in patients with biventricular compared to the control group (no exercise training)

Conditions

Univentricular Heart; Congenital Heart Disease; Lymphatic Abnormalities; Functional Capacity; Exercise Training; Quality of Life

Keywords

Lymphatic dysfunction; Near-Infrared Fluorescence Imaging; Fontan circulation; Plethysmography; Functional capacity; Aerobic exercise; Cardiac rehabilitation; Capillary filtration; Exercise training

Outcome Measures

Primary Outcomes (3)

• Assessing Peripheral Lymphatic Function Using Near-Infrared Fluorescence Imaging: Contraction Frequency Analysis over a 6-Minute Baseline

  Change in peripheral lymphatic function will be evaluated by Near-Infrared Fluorescence Imaging expressed by Contraction frequency (minute-1). A contraction was defined as a visual validation of a packet moving through a Regions of interests (ROI) placed on each measurable vessel and/or increase in the intensity signal displayed in the LabVIEW program. Contractions were counted over the obtained 6-min baseline.

  After 8 weeks of exercise training program or usual rotine

• Quantifying Peripheral Lymphatic Function through Near-Infrared Fluorescence Imaging: Assessment of Packet Velocity (cm/s) between ROIs.

  Change in peripheral lymphatic function will be evaluated by Near-Infrared Fluorescence Imaging expressed by Packet velocity (cm/s). Two ROIs were placed 5-10 cm apart on each vessel in the baseline sequence. Packages moving continuously through both ROIs were included in the calculations. The distance between the two ROIs was divided by the time difference between the packet passing each ROI.

  After 8 weeks of exercise training program or usual rotine

• Assessing Peripheral Lymphatic Function through Near-Infrared Fluorescence Imaging: Determination of Pumping Pressure (mmHg).

  Change in peripheral lymphatic function will be evaluated by Near-Infrared Fluorescence Imaging expressed by Pumping pressure (mmHg). Pumping pressure was determined by occluding lymphatic vessels using a Hokanson sphygmomanometer cuff (Marcom Medical Denmark). A tourniquet was placed distally to the sphygmomanometer cuff to prevent any lymphatic flow and allowing manual emptying of the lymphatic vessels under and above the cuff, which be inflated to 80 mm Hg (Hokanson E20 Rapid cuff inflator, Hokanson AG101 air source, SC10 cuff; Marcom Medical, Denmark) and the tourniquet was released allowing lymph flow up to the distal border of the cuff. Then, the cuff pressure was reduced with 5 mm Hg every 5th min until the fluorescent dye passed under the inflated cuff at which point the reached pressure level was noted as the pumping pressure.

  After 8 weeks of exercise training program or usual rotine

Secondary Outcomes (4)

• Assessment of Capillary Filtration Rate Using Venous Occlusion Plethysmography

  After 8 weeks of exercise training program or usual rotine

• Functional capacity assessment 1

  After 8 weeks of exercise training program or usual rotine

• "Functional Capacity Assessment through Cardiopulmonary Exercise Test: Predicted Peak VO2 (%) as an Indicator of Training Program Effectiveness

  After 8 weeks of exercise training program or usual rotine

• Assessment of Quality of Life Using Short Form 36 Questionnaire: A Multi-Domain Analysis with Scores Ranging from 0 to 100

  After 8 weeks of exercise training program or usual rotine

Study Arms (2)

Fontan Group - Exercise Training

EXPERIMENTAL

Online rehabilitation: 36 sessions of aerobic exercise training for two months

Other: Exercise training

Fontan Control Group - No Exercise Training

NO INTERVENTION

Patients will not participate in the exercise program and will continue with their usual routine.

Interventions

Exercise training OTHER

Aerobic and light muscle resistance exercise by online cardiovascular rehabilitation

Fontan Group - Exercise Training

Eligibility Criteria

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

You may qualify if:

• Fontan circulation
• Age above 18 years
• Agreeing to participate in the study and signing the informed consent form.

You may not qualify if:

• Motor alterations make it impossible to perform the cardiopulmonary test
• Mental illness
• Syndromes.

Sponsors & Collaborators

• University of Sao Paulo: lead
• Fundação de Amparo à Pesquisa do Estado de São Paulo: collaborator
• Copenhagen University Hospital, Denmark: collaborator
• University of Aarhus: collaborator

Study Sites (1)

Instituto do Coracao, Faculdade de Medicina da Universidade de Sao Paulo

São Paulo, São Paulo, 05403900, Brazil

Location

MeSH Terms

Conditions

Univentricular Heart; Heart Defects, Congenital; Lymphatic Abnormalities

Interventions

Exercise

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Two groups, one of them (10) will be submitted to an exercise program, and the other (10) will be maintained usual care.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Model Details: A longitudinal clinical trial, controlled and no-randomized. Intervention: Exercise (aerobic and light muscle resistance exercise)

Study Record Dates

• First Submitted: November 17, 2022
• First Posted: July 7, 2023
• Study Start: September 26, 2022
• Primary Completion: December 22, 2022
• Study Completion: December 22, 2022
• Last Updated: July 28, 2023

Record last verified: 2023-07

Locations

BR (1)