Efficacy of a High-intensity Physical Activity Program on Renal Function in High Risk Patients With Type 2 Diabetes (ACTIDIANE)

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

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.

Study Overview

• Status: Terminated
• Conditions: Diabetic Kidney Disease; Type2 Diabetes
• Intervention / Treatment: Other: HIPA; Other: Counseling PA

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.

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Liège, Belgium
    • Hospital of Liège
• France
  • Besançon, France
    • Besançon Hospital
  • Bordeaux, France, 33000
    • Bordeaux University Hospital
  • Caen, France, 14033
    • Caen University Hospital
  • Chartres, France
    • CH Chartres
  • Clermont Ferrand, France, 63000
    • Clermont ferrand University hospital
  • Corbeil-Essonnes, France, 91100
    • CHG Sud Francilien
  • Dijon, France, 21000
    • CHU Dijon
  • Lille, France, 59000
    • CHU Lille
  • Lyon, France, 69229
    • CHU de Lyon
  • Montpellier, France
    • CHRU
  • Nancy, France, 54000
    • CHU Nancy
  • Nice, France, 06003
    • CHU de NICE
  • Paris, France, 75651
    • Hopital Pitie Salpetriere
  • Paris, France, 75000
    • Bichat University Hospital
  • Paris, France, 75000
    • La Riboisière Hospital
  • Poitiers, France, 86000
    • Poitiers University Hospital
  • Strasbourg, France, 67000
    • CHU Strasbourg
  • Toulouse, France, 31000
    • CHU Toulouse
  • Tours, France, 37044
    • CHU de TOURS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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. The sessions will be preferably performed in sports gyms but if required can also be performed online with supervised coaches, trained for the study.	Other: HIPA; inclusion in a program with 2 weekly sessions of structured physical activity of 1 hour in a dedicated structure, under the supervision of a graduated coach. First 3 months : physical reconditioning 3 months and after: alternating sessions of physical strengthening and intermittent high-intensity physical activity Adaptation of the intensity of the program according to evaluation tests every 3 months
Active Comparator: Control group; Counseling of physical activity according to recommendations from the working group on Physical Activity of the SFD (French Language Diabetes Society).	Other: Counseling PA; Counseling of physical activity according to recommendations from the working group on Physical Activity of the SFD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal Function Decline	Estimated glomerular filtration rate slope computed within 2 years, evaluated with the cystatin-derived CKD-EPI formula At least 3 available determinations of estimated glomerular filtration rate will be required to perform the calculation of the slope	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ESRF	Incidence of end-stage renal failure requiring renal replacement therapy	2 years
Number of patients with a decrease in eGRF	Number of patients with a decrease in eGRF greater than 40% of baseline value	2 years
All cause death	Number of patients who died during the study (all cause)	2 years
Cardiovascular death	Cardiovascular death as proposed by the ICD-10 classification	2 years
Renal death	Renal death as defined as a situation where renal replacement therapy could be used but was not applied	2 years
MACE	MACE : major adverse cardiovascular endpoints : first occuring among cardiovascular death, myocardial infarction and stroke	2 years
Severe congestive heart failure	Severe congestive heart failure requiring hospitalization, adjudicated by a study outcome committee	2 years
Coronary artery disease	Coronary artery disease : myocardial infarction and/or coronary artery revascularizaton	2 years
Quality of life EQ-5D3L	Quality of life : assessed by using EQ-5D3L questionnaire	2 years
Male/Female lower urinary tract symptoms (LUTS)	Male/Female lower urinary tract symptoms : assessed by using M/F LUTS questionnaire	2 years
Safety of the intervention	including : adverse events, foot ulceration requiring medical advise, musculoskeletal disorders, hypoglycemia	2 years
Quality of life SF12	Quality of life : assessed by using SF12 questionnaire	2 years
Safety of HIPA performed by e-coaching in the context of COVID infection	AE and SAE will be carefully reviewed to assess if the HIPA sessions are safe as performed with e-coaching/ telephone-coaching during lock-down due to the COVID-19 pandemics	2 years

Collaborators and Investigators

• Sponsor: Poitiers University Hospital
• Collaborators: Hospices Civils de Lyon; Centre Hospitalier Universitaire Dijon; University Hospital, Montpellier; Central Hospital, Nancy, France; University Hospital, Bordeaux; University of Liege; University Hospital, Clermont-Ferrand; University Hospital, Caen; Centre Hospitalier Universitaire de Nice; Centre Hospitalier Universitaire de Besancon; University Hospital, Toulouse; University Hospital, Lille; Nantes University Hospital; Groupe Hospitalier Pitie-Salpetriere; Centre Hospitalier Sud Francilien; University Hospital, Tours; Hopital Lariboisière; University Hospital, Strasbourg; Bichat Hospital; HOSPITAL, CHARTRES

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2018
• Primary Completion (Actual): July 28, 2023
• Study Completion (Actual): July 28, 2023

Study Registration Dates

• First Submitted: April 26, 2017
• First Submitted That Met QC Criteria: June 9, 2017
• First Posted (Actual): June 12, 2017

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Diabetes; Renal function decline; High-intensity physical activity
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Complications; Diabetes Mellitus, Type 2; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: ACTIDIANE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: sharing policy is under the responsibility of the scientific committee who will organise this point Any request can be posted to the PI in the meantime.
• IPD Sharing Time Frame: pending
• IPD Sharing Access Criteria: pending

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No