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

Quality of Life Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05934578
• Other study ID #: CAAE 61404222.6.0000.0068
• Status: Completed
• Phase: N/A
• Start date: September 26, 2022
• Est. completion date: December 22, 2022

Study information

• Verified date: July 2023
• Source: University of Sao Paulo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Description:

The study population is patients submitted to Fontan operation to treat complex congenital heart disease (univentricular circulation), who are followed at InCor Heart Institute in Sao Paulo.

The investigators will perform all measures baseline and after 36 sessions of aerobic exercise and light resistance (exercise group) or after eight weeks in usual care (control group).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 22, 2022
• Est. primary completion date: December 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Fontan circulation

• Age above 18 years

• Agreeing to participate in the study and signing the informed consent form.

Exclusion Criteria:

• Motor alterations make it impossible to perform the cardiopulmonary test

• Mental illness

• Syndromes.

Related Conditions & MeSH terms

• Congenital Heart Disease
• Exercise Training
• Functional Capacity
• Heart Defects, Congenital
• Heart Diseases
• Lymphatic Abnormalities
• Quality of Life
• Univentricular Heart

Intervention

Other:
• Exercise training
Aerobic and light muscle resistance exercise by online cardiovascular rehabilitation

Locations

Country	Name	City	State
Brazil	Instituto do Coracao, Faculdade de Medicina da Universidade de Sao Paulo	São Paulo	Sao Paulo

Sponsors (4)

Lead Sponsor	Collaborator
University of Sao Paulo	Copenhagen University Hospital, Denmark, Fundação de Amparo à Pesquisa do Estado de São Paulo, University of Aarhus

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Assessment of Capillary Filtration Rate Using Venous Occlusion Plethysmography	The capillary filtration rate (CFR) can be evaluated using venous occlusion plethysmography. CFR is measured using a strain gauge plethysmography setup (Hokanson EC6 and E20; Marcom Medical, Denmark) connected to a PC via an analog-to-digital converter (ADInstruments, UK). The measurements were analyzed using Labchart 7 software.; The procedure involves placing a cuff around the right calf, conducting venous congestion applying pressures ranging from 20 to 70 mm Hg each 3 min. A strain gauge was placed on the widest circumference of the calf to record an increase in volume.; The CFR was measured as the slope of the time-volume change (%) curve at a steady state at the end of each pressure phase. Measurements were taken at 10 mm Hg pressure intervals from 20 to 70 mm Hg.	After 8 weeks of exercise training program or usual rotine
Secondary	Functional capacity assessment 1	Change in functional capacity will be performed by cardiopulmonary exercise test and will be expressed by Peak VO2 (mL/kg/min). After the training program, an increase in the peak VO2 value between 5 to 10% is expected in relation to the baseline value	After 8 weeks of exercise training program or usual rotine
Secondary	"Functional Capacity Assessment through Cardiopulmonary Exercise Test: Predicted Peak VO2 (%) as an Indicator of Training Program Effectiveness	Change in functional capacity will be performed by cardiopulmonary exercise test and will be expressed by Predicted Peak VO2 (%). After the training program, an increase in the predicted peak VO2 value between 5 to 10% is expected in relation to the baseline value.	After 8 weeks of exercise training program or usual rotine
Secondary	Assessment of Quality of Life Using Short Form 36 Questionnaire: A Multi-Domain Analysis with Scores Ranging from 0 to 100	Changes in quality of life will be measure by Short Form 36 questionnaire by 8 domains: Physical functioning, Physical role functioning, body pain, general health, vitality, social functioning, emotional role functioning, mental health. The quality of life classification for each domain is typically measured on a scale of 0 to 100, where a score close to 100 indicates a higher or superior quality of life, while a score near 0 suggests a lower or poorer quality of life.	After 8 weeks of exercise training program or usual rotine