Sickle Cell Trait and Exercise, Effect of Hot Environment (TDex)

July 18, 2019 updated by: Sophie Antoine-Jonville, University of the French West Indies and French Guiana

Metabolic and Vascular Response to Exercise in Sickle Cell Trait Carriers: Effect of Hot Environment

The heterozygous form of sickle cell disease is clinically asymptomatic. Nevertheless, it was observed that, the sickle cell trait is associated with serious medical complications especially during intense physical efforts. Moreover, the exposure to a hot environment (tropical climate) is suspected to be a determining factor in the occurrence of these medical complications.

However, the relationship between sickle cell trait and death during effort is not well established. Furthermore, the cascade of events that usually cause sickle cell crisis such as red blood cells sickling and rhabdomyolysis and which affect microcirculation are not known.

Our main objective in this study is to verify whether young healthy active men with sickle cell trait have reactive hyperemia to their hemoglobinemic condition during exercise; to identify the contribution of hot environment on these possible disturbances; and to determine underlying mechanisms.

In addition, disturbances in the regulation of glucose metabolism in healthy subjects under hot environment have been reported, marked by a significant increase in postprandial blood glucose. Therefore, this project is also intended to assess the contribution of the disturbance of glycoregulation during exercise under hot environment in active sickle cell trait carriers. The imbalance of pro and anti oxidant agents, the adhesion and inflammation markers will also be evaluated.

Results of this study will allow a better understanding of physio-pathological mechanisms leading to vascular accidents during exercise under tropical climate in young healthy sickle cell trait carriers; and to identify physical activity programs and nutritional interventions adapted to patients with sickle cell disease under hot environment.

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

Introduction

The sickle cell disease is an inherited disorder characterized by abnormal hemoglobin called hemoglobin S or sickle hemoglobin in red blood cells of subjects. The homozygous form (hemoglobin SS) causes sickle cell anemia and is the most severe kind of sickle cell disease. Hemoglobin SC disease and hemoglobin Sβ thalassemia are two other common forms of sickle cell disease. The sickle cell trait carriers are person who inherited the hemoglobin S from one parent and a normal hemoglobin A from the other (heterozygous AS). These people are generally healthy. However, more and more cases of serious complications have been reported, especially during efforts and stays at high altitude like hemorheological and microcirculatory disturbances, and rhabdomyolysis. Increased percentage of red cell sicking was observed in sickle cell trait (AS) carriers compared to normal individual after 45 min of walking at 33°C of temperature. AS individuals also showed an impairment in red blood deformability at rest, at the end, and 24 hours after maximal exercise as compared to normal individuals AA, showing the vulnerability of red blood cells of these seemingly healthy subjects. The stiffness of red blood cells along with blood viscosity also increased in AS group compared to AA group, as consequence the risk of vascular accidents increases. In athletes and military warfighters, an exercise collapse and sudden death associated with sickle cell trait has been observed. Several cases of sudden death in AS individuals have been reported by many authors during exercise, however the exact causes remain very poorly understood.

As constraints related to exercise in tropical climate, it was observed a reduction of power and volemia due to dehydration, diversion of blood volume to the cutaneous territories. It was also reported an impairment of carbohydrate metabolism.

Our objectives in this work are:

  • To characterize the microvascular response to exercise in a hot environment in sickle cell trait active young adults,
  • To highlight biological mechanisms underlying any microvascular response specificities of the sickle cell trait carriers,
  • To describe the vascular consequences of postprandial metabolic disturbances induced by exercise in hot environment,
  • To understand fasting and post-prandial glucose metabolism at rest, during and after exercise,
  • To test the recovery in a neutral thermal environment (22 °C) as a means of normalizing post-exercise vascular function.

Experimental protocol

Thirty male volunteers (15 healthy: AA and 15 sickle cell trait carriers: AS) non-smoking, aged 18-30 years, BMI between 19 and 25kg/m2 living in the Caribbean for at least 6 months will be enrolled in the study. All subjects will be in good health physically active (≥ 3h/week) with no history of heat stroke during exercise. They are not taking any medications and are not regularly consume alcohol.

Participants will be subjected to four experimental sessions:

  1. A familiarization session at fasting in a warm environment (33 °C) in which resting parameters like reactive hyperemia index, tympanic temperature, heart rate, cerebral and muscular oxygenation, pulse wave velocity and electrocardiogram (ECG) will be measured. Then a test of the intensity of exercise (VO2max) will be performed followed by a medical interview.

    The other 3 sessions will be performed early in the morning at fasting with 45 minutes of exercise on ergocycle. The exercise includes 15 minutes of warm up, then participants will be asked to pedal as fast as possible for 6 seconds. The test of 6 seconds will be repeated twice or more with recovery each time. During exercise, hydration will be controlled (2.5 ml water / kg every 15 minutes), oxygen consumption will be measured; and microvascular function and blood samples taken at different times of experiment in each session (T0, T60, T75, T90, T120). The design of this study is a crossover trial divided into 3 sessions presented in randomized order:

  2. Exercise performed in hot environment (33 °C) with recovery in the same environment.
  3. Exercise and recovery performed in a control (thermoneutral) environment (22 °C)
  4. Exercise performed in a hot environment (33 °C) with recovery in a thermoneutral environment (22 °C).

At the end of each session, a standardized meal will be given to each participant.

This study will be conducted in accordance with the guidelines developed in the Declaration of Helsinki, and all procedures were approved by the Committee for the Protection of Persons East-III. Written informed consent will be obtained from all participants.

Biochemical procedures

Blood samples will be use for hemorheological tests (viscosity of blood, stiffness, aggregability and sickling of red cells etc.) Dosage of creatine kinase (CK-MM, MB), myoglobin and troponin will be performed to assess the degree of rhabdomyolysis and the integrity of heart.

Glycemia and lactatemia will be determined using strips. Cortisol, insulin, adrenalin, glucagon and lactate dehydrogenase (LDH) assays will be performed using appropriated kits.

Plasma inflammatory profile will be determined by measuring markers such as myeloperoxidase (MPO), malondialdehyde (MDA), advanced oxidation protein products (AOPP), nitrotyrosin, and endothelin-1 using appropriated kits.

Adhesion molecules such as VCAM-1, ICAM-1 and P-selectin will be measured using ELISA kit from Diaclone or Eurobio.

The oxidative stress on red blood cells will be assessed by measuring glutathione ratio GSSH/GSSG, superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx).

Statistical analysis Data will be expressed as means with their standard errors. Statistical analyses will be performed with SPSS for MAC and p < 0·05 considered statistically significant.

All the data will be analysed by using repeated-measures ANOVA followed by Post hoc comparisons with the Student's paired t test. The tests of Kolmogorov-Smirnov, Newman Keuls and Duncan will be applied as appropriate.

Expected outcomes

  • Better understanding of physio-pathological mechanisms leading to severe vascular events following physical exercise in tropical climate in healthy sickle cell carriers.
  • Opening of tracks for identification of physical activity programs and nutritional interventions adapted to sickle cell patients in hot environment.
  • Understanding of mechanisms leading to disturbances of glucose metabolism under tropical climate in AA and in AS subjects.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Pointe-à-Pitre, Guadeloupe, 97157
        • ACTES laboratory

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 30 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • BMI between 19 and 25kg/m2,
  • Be living in the Caribbean for at least 6 months health
  • Be physically active (≥ 1350 METs/week)
  • No history of heat stroke during exercise
  • No taking any medications
  • Not regularly consuming alcohol
  • Have the ability and willingness to issue consent written, free and enlightened

Exclusion Criteria:

  • Have any other hemoglobinemic status than AA or AS.
  • Weight gain or loss of more than 2 kg in the last 6 month.
  • Food allergy to any of ingredients coming into the composition of test meals or that may result from a cross-contamination during manufacture: eggs and eggs products, gluten, milk and milk-based products (including lactose), soybean and soy products, fruit hulls (almonds, hazelnuts, walnuts, cashew nuts, pecan, macadamia, Brazil, Queensland, pistachios) and products made of these fruits.
  • Monitoring a particular diet
  • Any chronic metabolic pathology, cardiovascular, neurovascular, renal, respiratory, neuromuscular, musculoskeletal or articular known
  • Any disorder of the ear (infections, tumors, perforated eardrums, polyps)
  • Any infectious disease or inflammatory and infectious condition

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AS and AA
Participants will be submitted to 45 minutes of exercise on ergocycle.
The exercise includes 15 minutes of warm up, then participants will be asked to pedal as fast as possible for 6 seconds. The test of 6 seconds will be repeated twice or more with recovery each time

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microvascular function
Time Frame: 2 hours
Reactive hyperemia index (arbitrary units) will be assessed at rest, during exercise and during recovery in hot and thermoneutral environment
2 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Oxidative stress
Time Frame: 3 months
Glutathione ratio GSSH/GSSG
3 months
Inflammation
Time Frame: 3 months
Myeloperoxidase (MPO)
3 months
Adhesion molecules
Time Frame: 3 mois
VCAM-1
3 mois
Hemorheology
Time Frame: 24 hours
hematocrit
24 hours
Rhamdomyolysis
Time Frame: 3 months
Creatine kinase
3 months
Oxydative stress marker
Time Frame: 3 months
superoxide dismutase (SOD)
3 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glucose metabolism
Time Frame: 3 months
glucose
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Stéphane Henri, Dr, Laboratoire ACTES, EA 3596 UFR STAPS, University of the French West Indies and French Guiana
  • Study Director: Olivier Hue, PhD, Laboratoire ACTES, EA 3596 UFR STAPS, University of the French West Indies and French Guiana
  • Principal Investigator: Mona Hedreville, Dr, Unités Urgences cardiologiques CHU, Pointe-à-Pitre/Abymes 97159

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 25, 2017

Primary Completion (Actual)

July 1, 2019

Study Completion (Actual)

July 1, 2019

Study Registration Dates

First Submitted

July 16, 2019

First Submitted That Met QC Criteria

July 18, 2019

First Posted (Actual)

July 23, 2019

Study Record Updates

Last Update Posted (Actual)

July 23, 2019

Last Update Submitted That Met QC Criteria

July 18, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

All autors have to discuss together before to decide

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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