Clinical trial NCT04607096: Intermittent Fasting to Improve Insulin Secretion
Official title: Intermittent Fasting to Improve Insulin Secretion
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: PreDiabetes
Diabetes type2
Intermittent Fasting
Insulin Secretion
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
Collaborators: name: German Institute of Human Nutrition
name: Charite University, Berlin, Germany
name: University Hospital Carl Gustav Carus
name: University of Leipzig
name: Ludwig-Maximilians - University of Munich
name: University Hospital Heidelberg
name: University of Luebeck
name: German Diabetes-Center, Leibniz-Institut in Düsseldorf
name: German Center for Diabetes Research
First posted: 2020-10-28
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants wil either receive a control diet or join the intermittent fasting group stratified by glycemia (prediabetes/diabetes) as well as by subphenotype.
Primary purpose: TREATMENT

Brief summary: Type 2 diabetes (T2D) mellitus is a challenge for health care systems as the numbers increases constantly. In 2014, 422 million people had been living with diabetes worldwide. The absolute numbers of people with prediabetes have also grown substantially over 25 years worldwide. In Germany, about 10% of the population has T2D and another 21 % of the population has prediabetes.Overall, 16% of all deaths in Germany are attributable to type 2 diabetes. Macro- and microvascular complications of diabetes imply a significant threat for the patients and are already present in the prediabetic state. Short term and long term complications, the burden of treatment, and reduced quality of life are major burdens of the disease. Accumulating data indicate that currently recommended therapeutic diet regimens in patients with obesity and diabetes are not sustainable on the long term. Novel concepts are therefore urgently needed.

T2D occurs when insulin secretion from pancreatic beta-cells cannot sufficiently be increased to compensate for insulin resistance. Causes of beta-cell dysfunction are heterogeneous. In addition, the most important determinants of diabetes remission are the extend of weight loss and restoration of beta-cell function. In the course of diabetes progression, the inability to recover insulin secretion might identify the state of no return to normal glucose tolerance. It is therefore crucial to improve insulin secretion in treatment and prevention of diabetes. Up to now lifestyle intervention trials in prediabetes or pharmacological intervention trials in diabetes did not show improvement of insulin secretion after intervention. However, one recent small human trial shows that intermittent fasting (early time restricted fasting) is able to improve insulin secretion.Currently, there are no trials that examine the effect of intermittent fasting in individuals with a broad range of impaired glucose metabolism (from prediabetes to diabetes). Recently novel subtypes of diabetes and prediabetes with high risk for the early manifestation of diabetes complications have been identified. Currently, prevention strategies for this high risk individuals have not been examined yet. We will study for the first time the effectiveness of 4 weeks intermittent fasting on changes in insulin secretion capacity in subphenotypes of diabetes and in prediabetes.


Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) between 25 - 40 kg/m²
* Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures.
* Subjects with prediabetes (IFG and/or IGT, HbA1c 5,4 % - 6,4 %, subphenotype cluster 3 or 5) or
* Subjects with diabetes mellitus type 2 (diagnosis \< 1 year, HbA1c = 6,5 - 9 %, no medical treatment, subphenotype SIDD or SIRD)

Exclusion Criteria:

* Subjects with diabetes mellitus type 1 (GAD-, IA2-AB positive)
* Women during pregnancy and lactation
* Treamtent with any medication effecting on glucose metabolism like anti-diabetic drugs or steroids
* Subjects with a haemoglobin (Hb) ≤ 11.5 g/dl (for males) and Hb ≤ 10.5 g/dl (for females) at screening
* Any pancreatic disease
* Medical history of cancer and/or treatment for cancer within the last 5 years.
* Known current presence or history of severe neurological or psychiatric diseases, schizophrenia, bipolar disorder
* Known history of bariatric surgery
* Severe liver or kidney diseases (Alanine Aminotransferase (ALT \[SGPT\]), Aspartate Aminotransferase (AST \[SGOT\]) above 3 x upper limit of normal (ULN) or Glomerular Filtration Rate (eGFR) ≤ 60 ml/min (MDRD formula)
* Systemic infection (CRP \> 1 mg/dl)
* Severe diabetic complications like chronic kidney disease (CKD), proliferating retinopathy or symptomatic cardiovascular disease
* Presence of any contraindication for the conduct of an MRI investigation, such as cardiac pacemakers, ferromagnetic haemostatic clips in the central nervous system, metallic splinters in the eye, ferromagnetic or electronically operated active devices like automatic cardioverter defibrillators, cochlear implants, insulin pumps and nerve stimulators, prosthetic heart valves etc.
* Persons with limited temperature sensation and / or elevated sensitivity to warming of the body
* Persons with a hearing disorder or a increased sensitivity for loud noises
* Claustrophobia
* Participation in other clinical trials or observation period of competing trials up to 30 days prior to this study
* Refusal to get informed of unexpected detected pathological findings

Primary outcomes:
measure: Change in first phase insulin secretion.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
Secondary outcomes:
measure: Change in second phase insulin secretion.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in insulin sensitivity.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in BMI.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in liver fat content.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in pancreatic fat content.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in body fat content.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in visceral adipose tissue.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in subcutaneous adipose tissue.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
Other outcomes:
measure: Change in brain insulin sensitivity.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in resting energy expenditure (REE).
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in substrate oxidation.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in proinsulin processing.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in glucagon suppression.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
measure: Change in insuin clearance.
timeFrame: Before, after 4 weeks and after 24 weeks of lifestyle intervention.
Locations:
city: Berlin
country: Germany
facility: Charité Berlin - Department of Endocrinology and Metabolic Diseases
city: Dresden
country: Germany
facility: Universtiy Hospital Carl Gustav Carus
city: Duesseldorf
country: Germany
facility: German Diabetes Center
city: Heidelberg
country: Germany
facility: Heidelberg University Hospital - Department of Endocrinology and Metabolism
city: Leipzig
country: Germany
facility: University Hospital Leipzig - Clinic for Endocrinology and Nephrology
city: Luebeck
country: Germany
facility: University of Luebeck - Institute of Endocrinology and Diabetes
city: Munich
country: Germany
facility: Technical University of Munich - Else Kroener-Fresenius-Center for Nutritional Medicine
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen - Institute for Diabetes Research and Metabolic Diseases (IDM)
Study officials:
References: