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Trial record 4 of 28 for:    sickle cell | "Sickle Cell Trait"

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

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ClinicalTrials.gov Identifier: NCT04028791
Recruitment Status : Completed
First Posted : July 23, 2019
Last Update Posted : July 23, 2019
Sponsor:
Collaborator:
Institut National de la Santé Et de la Recherche Médicale, France
Information provided by (Responsible Party):
Sophie Antoine-Jonville, University of the French West Indies and French Guiana

Tracking Information
First Submitted Date  ICMJE July 16, 2019
First Posted Date  ICMJE July 23, 2019
Last Update Posted Date July 23, 2019
Actual Study Start Date  ICMJE September 25, 2017
Actual Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 18, 2019)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: July 18, 2019)
  • Oxidative stress [ Time Frame: 3 months ]
    Glutathione ratio GSSH/GSSG
  • Inflammation [ Time Frame: 3 months ]
    Myeloperoxidase (MPO)
  • Adhesion molecules [ Time Frame: 3 mois ]
    VCAM-1
  • Hemorheology [ Time Frame: 24 hours ]
    hematocrit
  • Rhamdomyolysis [ Time Frame: 3 months ]
    Creatine kinase
  • Oxydative stress marker [ Time Frame: 3 months ]
    superoxide dismutase (SOD)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: July 18, 2019)
Glucose metabolism [ Time Frame: 3 months ]
glucose
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Sickle Cell Trait and Exercise, Effect of Hot Environment
Official Title  ICMJE Metabolic and Vascular Response to Exercise in Sickle Cell Trait Carriers: Effect of Hot Environment
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:

All participants in each group (AA, AS) will carry out the following 3 sessions:

  1. Exercise performed in hot environment (33 °C) with recovery in the same environment
  2. Exercise and recovery performed in a control (thermoneutral) environment (22 °C),
  3. Exercise performed in a hot environment (33 °C) with recovery in a thermoneutral, environment (22 °C).
Masking: None (Open Label)
Primary Purpose: Screening
Condition  ICMJE
  • Sickle Cell Trait
  • Environmental Exposure
  • Adverse Effect
Intervention  ICMJE Other: 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
Study Arms  ICMJE Experimental: AS and AA
Participants will be submitted to 45 minutes of exercise on ergocycle.
Intervention: Other: Exercise on ergocycle
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 18, 2019)
21
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 1, 2019
Actual Primary Completion Date July 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 30 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Guadeloupe
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04028791
Other Study ID Numbers  ICMJE 2017-A02226-47
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: All autors have to discuss together before to decide
Responsible Party Sophie Antoine-Jonville, University of the French West Indies and French Guiana
Study Sponsor  ICMJE University of the French West Indies and French Guiana
Collaborators  ICMJE Institut National de la Santé Et de la Recherche Médicale, France
Investigators  ICMJE
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
PRS Account University of the French West Indies and French Guiana
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP