Clinical trial NCT03184662: Efficacy of a High-intensity Physical Activity Program on Renal Function in High Risk Patients With Type 2 Diabetes
Official title: Randomized Trial to Assess the Efficacy of a High-intensity Physical Activity Program on Renal Function Decline in High Risk Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Type2 Diabetes
Diabetic Kidney Disease
Keywords: High-intensity physical activity
Diabetes
Renal function decline
Lead sponsor: Poitiers University Hospital
Sponsor class: OTHER
Collaborators: name: University Hospital, Bordeaux
name: University Hospital, Clermont-Ferrand
name: Centre Hospitalier Universitaire Dijon
name: Centre Hospitalier Universitaire de Besancon
name: Hopital Lariboisière
name: Bichat Hospital
name: Centre Hospitalier Sud Francilien
name: University Hospital, Lille
name: Centre Hospitalier Universitaire de Nice
name: University Hospital, Caen
name: University Hospital, Toulouse
name: University Hospital, Tours
name: Nantes University Hospital
name: Groupe Hospitalier Pitie-Salpetriere
name: Hospices Civils de Lyon
name: University Hospital, Montpellier
name: University Hospital, Strasbourg
name: Central Hospital, Nancy, France
name: HOSPITAL, CHARTRES
name: University of Liege
First posted: 2017-06-12
Enrollment: 178
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Type 2 diabetes is a chronic condition whose prevalence is increasing globally. Kidney disease is a key complication of diabetes and is among the most common cause of end-stage renal disease, requiring renal replacement therapy.

It has been shown that the trajectory of renal function (estimated glomerular filtration rate - eGFR) is of great prognostic value for renal and cardiovascular endpoints in diabetic patients. However the clinical use of this prognostic marker is not associated to date with a clear therapeutic intervention, effective in patients with type 2 diabetes identified with this biomarker.

In France, type 2 diabetes patients have twice less physical activity than non-diabetic persons. Recently, it has been published that physical activity was associated with an improvement of renal risk in patients with type 2 diabetes, recruited from the LOOK-AHEAD study. It was demonstrated that high-intensity physical activity (HIPA) can have several additional advantages over moderate-intensity, on blood pressure improvement, and cardiovascular risk profile modification. In addition, this procedure was shown to be safe in patients with high cardiovascular risk.

We plan to perform a randomized intervention comparing a structured program of high-intensity physical activity (HIPA) vs standard recommendations for physical activity on renal function decline (primary outcome) and mortality, renal and cardiovascular endpoints, patients' safety and quality of life (secondary outcomes). Study participants will be patients with established type 2 diabetes and a high renal risk, identified by rapid renal function decline, defined as a eGFR slope below -5ml/min per 1.73 m2/yr. The intervention is planned to last for 2 years.

Detailed description: I- Visit organisation

V1 (screening) informed consent / examination / inclusion and non-inclusion criteria / medical history M/F LUTS / EPICES score / ECG Serum creatinine determination

V2 (Randomization) examination / verification of participation criteria / randomization Cystatin C collection / Biology Hypoglycemia notification / QAPPA / RPAQ / NAQA / Questionnaires (EQ-5D3L, SF12, Rosenberg Self esteem) / Accelerometer (ancillary) / Impedance-meter (ancillary) 6-minute step test / 10-meter walk test

V3 (1 month) examination / Hypoglycemia notification / QAPPA / RPAQ / Accelerometer (ancillary)

V4 (3 months) examination / Hypoglycemia notification / QAPPA / RPAQ / Questionnaires (EQ-5D3L, SF12, Rosenberg Self esteem) / Accelerometer (ancillary) 6-minute step test Biology

V5 (6 months) examination / Hypoglycemia notification / QAPPA / RPAQ / Questionnaires(EQ-5D3L, SF12, Rosenberg Self esteem) / Accelerometer (ancillary) 6-minute step test Cystatin C collection / Biology

V6 (12 months) examination / Hypoglycemia notification / QAPPA / RPAQ / NAQA / M/F LUTS / Questionnaires(EQ-5D3L, SF12, Rosenberg Self esteem) / ECG /Accelerometer (ancillary) / Impedance-meter (ancillary) Cystatin C collection / Biology 6-minute step test / 10-meter walk test

V7 (18 months) examination / Hypoglycemia notification / QAPPA / RPAQ / Questionnaires(EQ-5D3L, SF12, Rosenberg Self esteem) / Accelerometer (ancillary) Cystatin C collection / Biology 6-minute step test

V8 (24 months) / premature discontinuation examination / Hypoglycemia notification / QAPPA / RPAQ / NAQA / M/F LUTS / Questionnaires (EQ-5D3L, SF12, Rosenberg Self esteem) / ECG / Accelerometer (ancillary) / Impedance-meter (ancillary) 6-minute step test / 10-meter walk test Cystatin C collection / Biology

II- Recruitment criteria Inclusion

* Age : 45 and higher
* Female or male
* Type 2 diabetes with diabetes typing according to widely-accepted clinical and biological criteria \[3\].
* Subject able to practice physical activity. This includes a normal exercise test with or without anti-ischemic drugs, performed in the preceding 6 months or short before randomization. A certificate of no contre-indication for PA is to be delivered prior to randomization.
* With at least 3 available creatinine measurements in the 6 to 24 preceding months showing a rapid renal function decline defined as an eGFR slope below -5 ml/min/yr
* Estimated GFR equal to or higher than 30 ml/min/1.73m², defined by the CKD-EPI formula, at inclusion visit

Non inclusion

* Age strictly lower than 45 years
* Indication for cardiovascular rehabilitation (notably patient with ischemic heart disease or coronary revascularisation)
* Treatment with systemic NSAIDs or corticosteroids
* Lower limb amputation (above trans-metacarpal)
* Active proliferative retinopathy (risk of bleeding in case of effort)
* Contra-indication for the participation to PA:

  * Severe non-operated valvulopathy
  * Uncontrolled hypertension \> 180/110 mmHg
  * Thrombus in the left ventricular cavity
  * Unstable coronaropathy, according to physician
  * NYHA stage IV heart failure
* Any condition that would jeopardize patient's safety or would affect the conduct of the study
* Pregnant or breast-feeding women or women of child-bearing potential without effective contraception during the study
* Any situation associated with unreliable cystatin-C determinations, according to patient medical history: HIV positivity, melanoma and thyroid dysfunction
* Simultaneous participation to any interventional study able to interfere with the current study endpoints
* Patients not registered to the social security
* Protected adults (under guardianship and trusteeship)
* Subject unable to express their consent (due to intellectual/mental incapacity)

III- Intervention HIPA group Twice weekly physical activity session in a dedicated structure, supervised by a graduated coach, alternating sessions of strengthening and intermittent HIPA, allowing a mixed stimulation of neuro-muscular and cardiovascular systems, and regular (every 3 months) adjustment of the intensity of the program.

Control group Counseling of physical activity according to recommendations from the working group on Physical Activity of the SFD (French Language Diabetes Society) supported by patient's oriented leaflet.

IV- Handling with the COVID-19 pandemics

The COVID-19 pandemics has modified the shape of the study with

* difficulties to comply with the study plan, including recruitment pace. Visits can be postponed if required but investigators are encouraged to follow the initial plan. The time between randomization and V3 (1 month) and V4 (3 months) can sometimes be too short and it is acceptable to perform this visit by phone or even to cancel it.
* difficulties to comply with physical activity (PA) plan. As PA facilities have been locked down in the pandemics context, the sports committee of the ACTIDIANE study has agreed to move attendances to the gym to some remote PA sessions, via websession or if not possible, via telephone coaching sessions.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes
* Rapid renal decline function (yearly loss of eGFR over -5ml/min/1.73 m2) in the 6 to 24 preceding months

Exclusion Criteria:

* Lower limb amputation
* Indication for rehabilitation program
* Contra-indication for physical activity
* Unstable angina, left atrial thrombus,
* Unstable thyroid function
* Corticosteroids treatment
* Long-term NSAIDs
* Simultaneous participation to any interventional study able to interfere with the current study endpoints

Primary outcomes:
measure: Renal Function Decline
timeFrame: 2 years
Secondary outcomes:
measure: Incidence of ESRF
timeFrame: 2 years
measure: Number of patients with a decrease in eGRF
timeFrame: 2 years
measure: All cause death
timeFrame: 2 years
measure: Cardiovascular death
timeFrame: 2 years
measure: Renal death
timeFrame: 2 years
measure: MACE
timeFrame: 2 years
measure: Severe congestive heart failure
timeFrame: 2 years
measure: Coronary artery disease
timeFrame: 2 years
measure: Quality of life EQ-5D3L
timeFrame: 2 years
measure: Male/Female lower urinary tract symptoms (LUTS)
timeFrame: 2 years
measure: Safety of the intervention
timeFrame: 2 years
measure: Quality of life SF12
timeFrame: 2 years
measure: Safety of HIPA performed by e-coaching in the context of COVID infection
timeFrame: 2 years
Other outcomes:
Locations:
city: Liège
country: Belgium
facility: Hospital of Liège
city: Besançon
country: France
facility: Besançon Hospital
city: Bordeaux
country: France
facility: Bordeaux University Hospital
city: Caen
country: France
facility: Caen University Hospital
city: Chartres
country: France
facility: CH Chartres
city: Clermont Ferrand
country: France
facility: Clermont Ferrand University Hospital
city: Corbeil-Essonnes
country: France
facility: CHG Sud Francilien
city: Dijon
country: France
facility: CHU Dijon
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: Chu de Lyon
city: Montpellier
country: France
facility: CHRU
city: Nancy
country: France
facility: CHU Nancy
city: Nice
country: France
facility: Chu de Nice
city: Paris
country: France
facility: Bichat University Hospital
city: Paris
country: France
facility: La Riboisière Hospital
city: Paris
country: France
facility: Hôpital Pitié Salpétrière
city: Poitiers
country: France
facility: Poitiers University Hospital
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: CHU de TOURS
Study officials:
References: