RANKL-GLYC: Impact of the Rapid Normalization of Chronic Hyperglycemia and the Practice of Moderate Physical Activity on the "Receptor Activator of Nuclear Factor-kappa B Ligand / Osteoprotégérine (RANKL / OPG) System in Patients Living With Type II Diabetes

Sponsor

Centre Hospitalier Sud Francilien (Other)

Overall Status

Recruiting

CT.gov ID

NCT04893135

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The rapid normalization of hyperglycemia can cause a neuropathy called Diabetes Treatment-Induced Neuropathy (NITD). This phenomenon induces the presence of hyper vascularization and inflammation in contact with the nerve ends.

In another register in patients living with diabetes, it has been observed the development of a rare and devastating complication for the joints called the so-called neuroarthropathy of Charcot (CN).

Condition or Disease	Intervention/Treatment	Phase
Type II Diabetes	Other: pratice physical activity	N/A

Detailed Description

In another register in patients living with diabetes, it has been observed the development of a rare and devastating complication for the joints called the so-called neuroarthropathy of Charcot (CN). The pathophysiology of CN is not completely known but there is an activation of markers of inflammation and bone remodeling, disruption of the osteoblast and osteoclast system, activation of the RANKL system (Receptor activator of nuclear factor-kappa B ligand) and its antagonist osteoprogesterin (OPG). Inflammation and peripheral hypervascularization therefore seem to be a common link between the two pathologies mentioned (NITD and CN). We have confirmation that the rapid correction of chronic hyperglycemia can trigger (not systematically) NITD, but what about the influence of this rapid correction on the appearance of CN. Furthermore, physical activity (PA) and exercise have long been recognized as the cornerstones of the prevention and management of chronic diseases, due to their beneficial effects on the clinical parameters of various diseases. The practice of PA has a preventive and therapeutic effect against osteoporosis (a disease in which the level of RANKL is particularly high), so there is in theory a preventive effect of the practice of physical activity on the development of CN.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Impact of the Rapid Normalization of Chronic Hyperglycemia and the Practice of Moderate Physical Activity on the "Receptor Activator of Nuclear Factor-kappa B Ligand / Osteoprotégérine (RANKL / OPG) System in Patients Living With Type II Diabetes

Actual Study Start Date :

Oct 11, 2021

Anticipated Primary Completion Date :

Jan 11, 2023

Anticipated Study Completion Date :

Jan 11, 2023

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: G1A Uncontrolled diabetes (HbA1c> 8.5%) over 6 months. In order to assess the effect of rapid correction of HbA1c on RANKL levels, without the practice physical activity
Experimental: G1B Uncontrolled diabetes (HbA1c> 8.5%) over 6 months. In order to assess the effect of rapid correction of HbA1c on RANKL levels, with the practice physical activity	Other: pratice physical activity treadmill walking : walk at a speed of 2.7 km.h-1 in 3 stages of 3 mins with an incline of 0%, 5% and 10%
No Intervention: G2 Controlled diabetes (HbA1c level <7%). This group will study the natural course of RANKL levels in balanced diabetic patients.

Arm

Intervention/Treatment

No Intervention: G1A

Uncontrolled diabetes (HbA1c> 8.5%) over 6 months. In order to assess the effect of rapid correction of HbA1c on RANKL levels, without the practice physical activity

Experimental: G1B

Uncontrolled diabetes (HbA1c> 8.5%) over 6 months. In order to assess the effect of rapid correction of HbA1c on RANKL levels, with the practice physical activity

Other: pratice physical activity

treadmill walking : walk at a speed of 2.7 km.h-1 in 3 stages of 3 mins with an incline of 0%, 5% and 10%

No Intervention: G2

Controlled diabetes (HbA1c level <7%). This group will study the natural course of RANKL levels in balanced diabetic patients.

Outcome Measures

Primary Outcome Measures

RANKL/OPG level [at 3 months]
RANKL/OPG level

Secondary Outcome Measures

Sudoscan measurement [at 3 months]
The Sudoscan non-invasively measures the ability of sweat glands to release chloride ions in response to an electrochemical stimulus on the palms of the hands and soles of the feet, areas with the highest density of sweat glands using four independent electrodes placed on the palms of the hands, soles of the feet which have a high density of sweat glands,

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Group G1:

Male or female patient aged 18 to 70, not practicing regular physical activity (Baecke score <10)
Patient with type 2 diabetes for at least 1 year
Patient treated with metformin +/- SU +/- DPP4 inhibitor +/- GLP1 analogue +/- insulin therapy
Patient insufficiently balanced under his current treatment with an HbA1c level> 8.5% for 6 months.
Patient able to practice physical activity on a regular basis
Patient having performed a coronary artery disease screening test in the year prior to inclusion
Woman of childbearing age with effective contraception put in place and monitored throughout the trial
Patient having given his consent to participate in the study and having signed an informed consent
Within the G1 group, a controlled 1: 1 randomization, stratified on age (≤65 years or> 65 years) and BMI (≤ 30 or> 30) will determine the inclusion of patients in the G1A group (correction of HbA1c) or G1B (correction of HbA1c + physical activity).

Group G2:

Male or female patient aged 18 to 70, not practicing regular physical activity
Patient with type 2 diabetes for at least 1 year
Patient treated with metformin +/- SU +/- DPP4 inhibitor +/- GLP1 analogue +/- insulin therapy
Patient balanced under his current treatment with an HbA1c level <7% for 6 months.
Women of childbearing potential with effective contraception put in place and monitored throughout the trial
Patient having given his consent to participate in the study and having signed an informed consent
Matching with the last patient included in group G1 on age (± 5 years), sex, duration of diabetes (± 2 years) and BMI (± 2kg / m2).

Exclusion Criteria:

Fetal and maternal pathologies requiring maturation Patient with type 1 diabetes
Patient with regular physical activity
History of severe cardiovascular pathologies (myocardial infarction, or acute coronary syndrome, or stroke in the past year)
Patient with a history of severe hypoglycemia in the 6 months preceding entry into the study and / or not experiencing hypoglycemia at all
Patient pregnant or likely to be
Severe obesity (BMI> 35kg / m2)
Other pathologies likely to interfere with the glycemic variation: in particular the use of corticosteroids during the study
Patient already having Charcot's neuroarthropathy or symptomatic autonomic neuropathy: orthostatic hypotension and / or gastro-paresis
Patient with preproliferative diabetic retinopathy
Patient having anti RANKL treatment
Subject under tutorship or curatorship
Subject not affiliated to social security.