Relative Energy Deficiency in Sport Multicenter Study

Study Overview
=================
Brief Summary
-----------------
Relative Energy Deficiency in Sport (RED-S) characterizes a range of negative health and performance outcomes that result from chronically low energy availability. RED-S concerns high performance junior and senior athletes across Canada and has a prevalence rate of 3-60%. Our ability to assess and diagnose RED-S remains poor. Accordingly, we aim to create the best parameters to diagnose and manage RED-S; along with information of the prevalence and severity across Canada and globally. These outcomes are expected to have a significant positive impact on the health and performance of Canadian athletes in preparation for the Olympic Games in 2022 and beyond.

Detailed Description
-----------------
Purpose: Our aim is to improve our understanding of the prevalence and symptoms of RED-S in international and Canadian athletes and para-athletes, along with developing screening tools and treatment protocols to manage RED-S in order to improve athlete health, availability and performance. Objectives: Assess the prevalence of self-reported RED-S health outcomes in international and Canadian elite female and male athletes and para-athletes as well as recreational athletes (Study A); Assess the prevalence and severity of measured standard/basic RED-S health outcomes including biomarkers and potential longitudinal (6-mo) tracking of outcomes across the Canadian Olympic and Paralympic Sport Institute Network (COPSI) (Study B); Implement a more advanced assessment, using novel RED-S assessment parameters in a smaller cohort of key athletes, including potential longitudinal tracking over a 6-mo period (Study C); Assess longitudinal changes and the treatment of RED-S symptoms across a 6-month follow-up period in a small cohort of elite Canadian athletes willing to partake in an 'holistic' RED-S treatment intervention arm (Study D); Utilize the data created from Studies A,B,C,and D to develop and validate potentially novel RED-S assessment parameters in order to further validate the 'new' IOC RED-S clinical assessment tool (CAT) version 2 to aid in the diagnosis of RED-S. Justification: This study will be the first to systematically assess the prevalence and severity of outcomes of RED-S in a large group of international and Canadian athletes and para-athletes (A), and within the COPSI network (B,C), utilising physiological and performance tests and training metrics for a more holistic assessment of potential outcomes (B,C,). This study will also aim to strengthen the literature regarding to the time-course of changes in these outcomes (B,C,D) and the efficacy of a simple nutritional intervention arm on these changes (D). Finally, this multicentre project will be the largest to date in Canada and globally, and the first to produce data on the prevalence of RED-S within the COPSI network (across A,B,C,D). Research Design: This is an observational study including online survey and physiological testing with potential for follow-up in a subset of athletes. A separate study arm (study D) will be an intervention arm with follow-up. Statistical analysis: Analysis will be a combination of basic statistics such as t-tests and ANOVA's, as well as more advanced statistical modelling (e.g. stepwise regression modelling, with first identifying collinearity among independent variables via the implementation of variance inflation factors (VIFs)) as well as questionnaire-based statistics and potentially principal components analysis (PCA) will be implemented. Physiological data will be plotted against survey data to create links between RED-S symptoms among various athlete groups (female vs male, able bodied vs disabled, sports groups, age categories, etc.)

Official Title
-----------------
Relative Energy Deficiency in Sport (RED-S) in International and Canadian High Performance Athletes: Prevalence, Health and Performance Implications

Conditions
-----------------
Sleep Hygiene, Health, Subjective, Nutrition Disorders, Athletic Injuries, Hormone Disturbance, Exercise-related Amenorrhea, Eating Disorders, Cardiovascular Abnormalities, Bone Fracture, Bone Loss, Weight Change, Body, Mental Health Wellness 1

Intervention / Treatment
-----------------
* Behavioral: Treatment of REDS using a holistic treatment arm


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: International or Canadian elite (National Sport Organization identified) and (Provincial Sport Organization / University varsity identified) Next Generation, or recreational athlete or para-athlete Female or male athlete or para-athlete currently and actively training for and racing in an Olympic sports event Age >15 years Exclusion Criteria: Under 15 years old Pregnant

Ages Eligible for Study
-----------------
Minimum Age: 15 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will be comprised of: 1) screening of athletes for symptoms of REDS; and 2) treating athletes diagnosed with REDS with a nutritional intervention
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Global screening of high-performance athletes for REDS<br>This arm collects data with an online survey to assess prevalence and signs and symptoms of REDS in elite female and male elite and recreational athletes and para-athletes over the age of 15 years across the world. | |
| No Intervention: Basic screening of Canadian high-performance athletes for REDS<br>In this study arm, varsity level to elite Canadian athletes and para-athletes will complete a baseline blood sample and potentially (where abnormalities are present) a follow-up 6 months later. | |
| No Intervention: Advanced screening of Canadian high-performance athletes for REDS<br>In this study arm, varsity level to elite Canadian athletes and para-athletes will complete a baseline test for bone density (DXA scans), resting metabolic rate and exercise testing. Potentially (where abnormalities are present) a follow-up 6 months later. | |
| Experimental: Treatment of Canadian athletes with REDS: a holistic intervention arm<br>In this arm, varsity level to elite Canadian athletes and para-athletes with REDS will participate in a nutritional intervention aiming to improve energy availability and thus, REDS status. | Behavioral: Treatment of REDS using a holistic treatment arm<br>* This arm aims to treat athletes with REDS symptoms by implementing a holistic, individualized nutrition intervention to improve energy availability and thus restore impaired body function due to REDS.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| REDS clinical assessment tool and REDS risk score | a combination of validated and semi-validated questionnaires | Baseline and possibly change after 6 months for a subset of athletes | 
| Menstrual function in females | via Low Energy Availability in Females Questionnaire (higher scores reflect higher risk of RED-S) and use of urinary ovulation strips to measure LH surge | Baseline and possibly change after 6 months for a subset of athletes | 
| Triiodothyronine concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Estrogen concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Testosterone concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Luteinizing hormone concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Follicle-stimulating hormone concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Sex-hormone binding globulin concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Hemoglobin concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Ferritin concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Serum iron concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Total iron binding capacity | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Iron saturation | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Total cholesterol concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| LDL cholesterol concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| HDL cholesterol concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Triglycerides concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Bone mineral density | Dual energy x ray scan of lumbar spine and femoral neck bone density | Baseline | 
| Resting metabolic rate | Assessment done with a metabolic cart by collecting respiratory gases | Baseline and possibly change after 6 months for a subset of athletes | 
| Aerobic capacity | maximal oxygen uptake test | Baseline and possibly change after 6 months for a subset of athletes | 
| Strength | Maximal strength tests | Baseline and possibly change after 6 months for a subset of athletes | 
| Insulin like growth factor 1 concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Resting heart rate | Heart rate monitor (Polar electro) | Baseline and possibly change after 6 months for a subset of athletes | 
| Blood pressure (systolic and diastolic) | Blood pressure monitor | Baseline and possibly change after 6 months for a subset of athletes | 
| Bone stress injury history | online questionnaire on type and number of injuries | Baseline and possibly change after 6 months for a subset of athletes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition | Via DXA or skinfold calipers | Baseline and possibly change after 6 months for a subset of athletes | 
| Complete blood count | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Insulin concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Glucose concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Cortisol concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| Prolactin concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| 25(OH)D concentrations | Venous blood samples | Baseline and possibly change after 6 months for a subset of athletes | 
| illness history | online questionnaire on frequency of illness in the past 24 months | Baseline and possibly change after 6 months for a subset of athletes | 
| Soft-tissue injury history | online questionnaire on the type and number of injuries in the past 24 months | Baseline and possibly change after 6 months for a subset of athletes | 
| Sleep hygiene | Athlete Sleep Screening Questionnaire (higher scores reflect sleep impairments) | Baseline and possibly change after 6 months for a subset of athletes | 
| Mental health | Depression, anxiety and stress scale 21 (higher scores reflect increased mental challenges) | Baseline and possibly change after 6 months for a subset of athletes | 
| Male athlete health | Low Energy Availability in Males Questionnaire (scoring is under development but higher scores reflect higher risk of REDS) | Baseline and possibly change after 6 months for a subset of athletes | 
| Gut health | Sections from the LEAF-Q (higher scores reflect higher risk of REDS) | Baseline and possibly change after 6 months for a subset of athletes | 
| Cardiac health | Questions from the Pre-Participation Examination questionnaire (higher scores reflect higher risk of cardiac symptoms) | Baseline and possibly change after 6 months for a subset of athletes | 
| Mood state | Brunel Mood Scales (higher scores reflect higher mood disturbance) | Baseline and possibly change after 6 months for a subset of athletes | 
| Eating disorder assessment | Eating Disorder Examination 3 (higher scores reflect higher risk of eating disorders) | Baseline and possibly change after 6 months for a subset of athletes | 
| History of weight change | online questionnaire | Baseline and possibly change after 6 months for a subset of athletes | 
| History of anemia | online questionnaire | Baseline and possibly change after 6 months for a subset of athletes | 
| REDS treatment arm | holistic nutrition based treatment of REDS symptoms including increasing energy availability via nutrition counselling | Individualised but likely 3-6 months |