Evolution of Total Energy Expenditure and Its Various Components in Active Rheumatoid Arthritis (RA)Treated With Anti-TNF Agents and Comparison With Healthy Subjects

Chronic inflammation in rheumatoid arthritis is associated with adiposity, sarcopenia, cachexia, reduced activity due to functional impairment, and anti-inflammatory drugs. Patients frequently gain weight when taking anti-tumor necrosis factor (TNF) medication, prompting questions about the underlying mechanism and long-term cardiovascular and metabolic tolerance associated with these drugs The primary objective of this study is to analyze the impact of anti-TNF treatment during the first year of administration on the energy metabolism of patients suffering from RA, assessed as an absolute value (before-after) and in comparison with a standard measured in healthy matched subjects.

Study Overview

• Status: Unknown
• Conditions: Active Rheumatoid Arthritis
• Intervention / Treatment: Behavioral: Energy metabolism of patients suffering from RA

Detailed Description

Few studies have been focused on the combined evolution of body composition, energy expenditure, physical activity, muscle performance, and nutritional intake in patients taking anti-TNFs.

This study's objective is to assess the impact of anti-TNF treatment during the first year of administration on the energy metabolism of RA patients, measuring variations in basal daily energy expenditure and per type of expenditure using indirect calorimetry with calorimetric chambers. Investigator also aim to define standardized values for RA patients compared to healthy matched controls and to be able to monitor the evolution of these different values during treatment compared to this standard.

This will be an exploratory study with a longitudinal follow-up of the cohort in patients treated in a market authorization context and involving a case/control study. Investigator judged the inclusion of healthy controls justified by the current lack of data comparing the different components of energy metabolism in active RA patients versus healthy subjects using calorimetric chamber measurement. The aim is to obtain reference values to situate RA-specific values in comparison before and after treatment. Investigator considered selecting controls from the RA patients unjustified given how essential it is to commence treatment in active RA cases (1 year with placebo not justifiable). A previously-treated inactive RA population with no inflammation would not be comparable to patients with active RA, and neither would a population with active RA treated with conventional treatment or a different biotherapy to anti-TNFs. Investigator also chose to perform a second assessment at 6 months without calorimetric chamber measurement but rather an indirect measurement using actimetry in order to limit costs and patients lost-to-follow-up due to treatment modification (failure or intolerance), all the while maintaining full assessment at 12 months. Scheduling the assessment at 12 months is justified by published studies' reports of delay before significant weight gain manifests, and enables us to maintain homogeneity as regards variations in physical activity and nutritional intake linked to seasonal changes.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Clermont-Ferrand, France, 63003
    • Chu Clermont-Ferrand
    • Principal Investigator: Anne TOURNADRE
    • Sub-Investigator: Martin SOUBRIER
    • Sub-Investigator: Yves BOIRIE
    • Sub-Investigator: Ruddy Richard
    • Sub-Investigator: Christophe MONTAURIER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• RA patients Women over 18 years old with proven active (DAS28 >3.2) RA, diagnosed based on ACR/EULAR 2010 criteria, receiving biological anti-TNF treatment for the first time.

Covered by social security. Capable of giving informed consent and acceding to the requirements of the study.

For high-resolution echocardiography: no hypertension, diabetes or history of cardiovascular disorders.

- Healthy volunteers (control group) The healthy female controls will be enrolled from the Centre de Recherche en Nutrition Humaine (CRNH) list of volunteers and matched to the RA patients according to age ±5 years and BMI class (<25; 25-30; >30).

Exclusion Criteria:

• Refusal to sign consent form.

  • Patients under guardianship or curatorship.
  • Previous exposure to biological treatment in the course of their disease.
  • Suffering from a condition potentially influencing energy metabolism: infection, cancer, diabetes, thyroid dysfunction, psychiatric disorder, current smoker, pregnancy.
  • High physical activity level, based on short-form IPAQ questionnaire.
  • Variations in weight exceeding 5% of body weight in the previous 6 months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 16 patients with active RA; Women over 18 years old with proven active (DAS28 >3.2) RA, diagnosed based on ACR/EULAR 2010 criteria, receiving biological anti-TNF treatment for the first time. Covered by social security. Capable of giving informed consent and acceding to the requirements of the study. For high-resolution echocardiography: no hypertension, diabetes or history of cardiovascular disorders.	Behavioral: Energy metabolism of patients suffering from RA; Energy metabolism of patients suffering from RA
Sham Comparator: 8 Healthy volunteers (control group); Healthy volunteers (control group) The healthy female controls will be enrolled from the Centre de Recherche en Nutrition Humaine (CRNH) list of volunteers and matched to the RA patients according to age ±5 years and BMI class (<25; 25-30; >30).	Behavioral: Energy metabolism of patients suffering from RA; Energy metabolism of patients suffering from RA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Continuous measurement of energy expenditure and cardiac rhythm in calorimetric chamber	Continuous measurement of energy expenditure and cardiac rhythm in calorimetric chamber for 36 hours: at rest, waking, during two physical activity sessions (treadmill walking at 4km/h for 30min), sleeping.	for 36 hours
Indirect assessment of energy expenditure	Indirect assessment of energy expenditure by measuring physical activity using home actimetry(Armband) under normal living conditions for 4 days and in the calorimetric chamber for calibration.	for 4 days
Nutritionist assessment of nutritional intake	Nutritionist assessment of nutritional intake during the 2 days preceding energy expenditure measurement.	during the 2 days preceding energy expenditure measurement.
Previously-scheduled tests for the RCVRIC protocol		at day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Indirect assessment of energy expenditure via measurement of physical activity using calibrated actimetry (Armband)	Indirect assessment of energy expenditure via measurement of physical activity using calibrated actimetry (Armband) at home in normal living conditions over 4 days.	at 6 months
Nutritionist evaluation of nutritional intake over 2 days		at 6 months
Previously-scheduled tests for the RCVRIC study protocol (M6):	DXA, pQCT, physical strength and performance, physical activity and nutrition questionnaires, cardiovascular risk, serum and urine bank research.	at 6 months

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Centre de Recherche en Nutrition Humaine d'Auvergne
• Investigators: Principal Investigator: Anne TOURNADRE, University Hospital, Clermont-Ferrand

Study record dates

Study Major Dates

• Study Start (Anticipated): November 30, 2017
• Primary Completion (Anticipated): October 31, 2019
• Study Completion (Anticipated): December 31, 2019

Study Registration Dates

• First Submitted: November 15, 2017
• First Submitted That Met QC Criteria: November 16, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): November 21, 2017
• Last Update Submitted That Met QC Criteria: November 20, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: CHU-365; 2017-A01654-49 (Other Identifier: 2017-A01654-49)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No