Clinical trial NCT01947595: Individualized Lifestyle Intervention in Subjects With Prediabetes
Official title: Prediabetes Lifestyle Intervention Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus Type 2
Keywords: diabetes mellitus type 2
impaired glucose tolerance
lifestyle intervention
body fat distribution
prevention
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: German Diabetes-Center, Leibniz-Institut in Düsseldorf
name: Endocrinology and Metabolic Diseases, Charité Berlin
name: German Institute of Human Nutrition
name: University Hospital Carl Gustav Carus
name: LMU München, medical clinic IV
name: University Hospital Heidelberg
First posted: 2013-09-20
Enrollment: 1145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this prospective randomized multicenter intervention study is to determine whether in the prevention of Diabetes an intensified lifestyle intervention is superior to a conventional lifestyle intervention in high risk non-Responder subjects. Further, the intensive phenotyping to determine subgroups with an increased risk for diabetes enables an individualized prevention and therapy of type 2 diabetes mellitus.

Detailed description: The study start with an intensive phenotyping at baseline (initial examination) to determine subjects with prediabetes. These high risk non-Responder are randomized in two arms (intensified vs normal lifestyle intervention)with equal number of subjects (n=250). The results are compared with each other at the end of the study.

The low risk Responder are randomized in two arms (normal vs. once lifestyle intervention = control group) with equal number of subjects (n=250).

After the screening at baseline the 12 month lifestyle intervention starts for lifestyle intervention groups. The different therapy groups are formed as described before. The subjects with intensified lifestyle intervention get 16 consultations, the subjects with normal lifestyle intervention get 8 consultations, the subjects of the control group get one consultation to learn more about a healthier lifestyle. During the whole study there is a continuous supervision from physician and nutritional advisers and the subjects have to document a nutrition and an exercise protocol as well as subjective measurements. At baseline, after 24 weeks and at follow up 1, 2 and 3 years later there is an elaborate metabolic characterization of all subjects (also the Responder groups) a 75 g venous oral glucose tolerance test (OGTT) as well as an analysis of the distribution of body fat confirmed by MR-Imaging and proton magnetic resonance spectroscopy by 3 T whole body imager.

Eligibility criteria: Inclusion Criteria:

* impaired fasting glucose (IFG)

  * fasting blood glucose 99-126 mg/dl

and/or

* impaired glucose tolerance (IGT)

  * 75 g OGTT 120 minutes: 139-200 mg/dl

Exclusion Criteria:

* current pregnancy or breastfeeding
* BMI \> 45 kg/m²
* Diabetes mellitus Typ 1 or 2
* serious disease e.g symptomatic coronary heart disease
* serious symptomatic malignant disease (weight loss \> 10% within the last 6 month)
* severe liver or kidney disease ( an increase in transaminases \> 3 times than the upper limit of the standardized range, GFR \< 50 ml/min/1,73m²)
* systemic infection (CRP \> 1 mg/dl)
* severe mental illness
* drug abuse
* treatment with steroids
* potentially incompliant subjects
* exclusion criteria for magnetic resonance tomography

  * any kind of metal in or on the body:

    * cardiac pacemakers
    * prosthetic heart valves
    * metal prosthesis
    * magnetic implanted metallic parts
    * contraceptive coil
    * metal fragments/ grenade shrapnel
    * fixed braces
    * acupuncture needles
    * insulin pump
    * intraport etc.
    * Field strength \> 3 Tesla further tattoos, permanent make-up
  * persons with limited thermosensory or heightened sensitivity to heating
  * persons where cardiovascular disease cannot be ruled out by examination
  * persons with heightened sensitivity to loud noise or diseases of the ear
  * used closed whole body scanner: claustrophobia

Additional for spirometry

* acute coronary syndrome
* higher cardiac arrhythmia
* decompensated heart failure
* acute carditis
* pulmonary embolism
* acute deep leg vein thrombosis ( phlebothrombosis)
* hyperthyroidism (TSH)
* hypokalemia

Primary outcomes:
measure: postprandial glycaemia (2h plasma glucose level of the 75 g oral glucose tolerance test (OGTT))
timeFrame: one year
Secondary outcomes:
measure: insulin sensitivity confirmed by 75 g oral glucose tolerance test (OGTT)
timeFrame: one year
measure: insulin secretion confirmed by 75 g oral glucose tolerance test (OGTT)
timeFrame: one year
measure: distribution of body fat confirmed by MR-Imaging and proton magnetic resonance spectroscopy by 3 T whole body imager
timeFrame: one year
Other outcomes:
measure: metabolic and genetic characterization to determine the risk of type 2 diabetes confirmed by case history, clinical examination, venous blood sampling, DNA isolation, standardised questionnaires, bio-electric impedance analysis (BIA)and ergospirometry
timeFrame: one year
measure: metabolic and genetic characterization to determine the non-response to lifestyle intervention confirmed by case history, clinical examination, venous blood sampling, DNA isolation, standardised questionnaires,BIA, ergospirometry
timeFrame: one year
Locations:
city: Berlin
country: Germany
facility: Deutsches Institut für Ernährungsforschung / Charité Berlin
city: Dresden
country: Germany
facility: University Hospital Dresden
city: Düsseldorf
country: Germany
facility: Deutsches Diabetes Zentrum
city: Munich
country: Germany
facility: Technische Universität München (TU Munich)
city: Munich
country: Germany
facility: Helmholtz Zentrum München
city: Munich
country: Germany
facility: Ludwig-Maximilians-University
city: Tübingen
country: Germany
facility: University Hospital Tübingen
Study officials:
affiliation: University Hospital Tuebingen
name: Andreas Fritsche, Prof. Dr. med
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Tübingen
name: Norbert Stefan, Prof.Dr.med.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wagner R, Eckstein SS, Fritsche L, Prystupa K, Horber S, Haring HU, Birkenfeld AL, Peter A, Fritsche A, Heni M. Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health. Front Endocrinol (Lausanne). 2022 Jun 29;13:892677. doi: 10.3389/fendo.2022.892677. eCollection 2022.
citation: Fritsche A, Wagner R, Heni M, Kantartzis K, Machann J, Schick F, Lehmann R, Peter A, Dannecker C, Fritsche L, Valenta V, Schick R, Nawroth PP, Kopf S, Pfeiffer AFH, Kabisch S, Dambeck U, Stumvoll M, Bluher M, Birkenfeld AL, Schwarz P, Hauner H, Clavel J, Seissler J, Lechner A, Mussig K, Weber K, Laxy M, Bornstein S, Schurmann A, Roden M, de Angelis MH, Stefan N, Haring HU. Different Effects of Lifestyle Intervention in High- and Low-Risk Prediabetes: Results of the Randomized Controlled Prediabetes Lifestyle Intervention Study (PLIS). Diabetes. 2021 Dec;70(12):2785-2795. doi: 10.2337/db21-0526. Epub 2021 Sep 16.