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Intermittent Fasting to Improve Insulin Secretion (IFIS)

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ClinicalTrials.gov Identifier: NCT04607096
Recruitment Status : Recruiting
First Posted : October 28, 2020
Last Update Posted : December 9, 2021
Sponsor:
Collaborators:
German Institute of Human Nutrition
Charite University, Berlin, Germany
University Hospital Carl Gustav Carus
University of Leipzig
Ludwig-Maximilians - University of Munich
University Hospital Heidelberg
University of Luebeck
German Diabetes-Center, Leibniz-Institut in Düsseldorf
German Center for Diabetes Research
Information provided by (Responsible Party):
University Hospital Tuebingen

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.


Condition or disease Intervention/treatment Phase
PreDiabetes Diabetes type2 Intermittent Fasting Insulin Secretion Behavioral: Intermittent fasting Behavioral: Control diet Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intermittent Fasting to Improve Insulin Secretion
Actual Study Start Date : April 8, 2021
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : March 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Prediabetic subjects - cluster 3
Presence of a cluster 3 phenotype will be examined according to the parameters described by Wagner et al.(Nat. Med. 2020).
Behavioral: Intermittent fasting
The intermittent fasting intervention consists of a decreased daily caloric intake of 400 kcal below individual requirements (Harris Benedict Formula) combined with early time restricted fasting according to the schema 16:8. fasting will be performed over 4 weeks.

Behavioral: Control diet
Control group will be advised to reduce daily caloric intake of 400 kcal below individual requirements (Harris Benedict formula)

Active Comparator: Prediabetic subjects - cluster 5
Presence of a cluster 5 phenotype will be examined according to the parameters described by Wagner et al.(Nat. Med. 2020).
Behavioral: Intermittent fasting
The intermittent fasting intervention consists of a decreased daily caloric intake of 400 kcal below individual requirements (Harris Benedict Formula) combined with early time restricted fasting according to the schema 16:8. fasting will be performed over 4 weeks.

Behavioral: Control diet
Control group will be advised to reduce daily caloric intake of 400 kcal below individual requirements (Harris Benedict formula)

Active Comparator: Patients with type 2 diabetes - subphenotype: Severe insulin-deficient diabetes (SIDD)
Presence of a SIDD phenotype will be examined according to the parameters de-scribed Ahlqvist et al. (Lancet Diabetes Endocrinol. 2018 May;6(5):361-369).
Behavioral: Intermittent fasting
The intermittent fasting intervention consists of a decreased daily caloric intake of 400 kcal below individual requirements (Harris Benedict Formula) combined with early time restricted fasting according to the schema 16:8. fasting will be performed over 4 weeks.

Behavioral: Control diet
Control group will be advised to reduce daily caloric intake of 400 kcal below individual requirements (Harris Benedict formula)

Active Comparator: Patients with type 2 diabetes - subphenotype: Severe insulin-resistant diabetes (SIRD)
Presence of a SIRD phenotype will be examined according to the parameters de-scribed Ahlqvist et al (Lancet Diabetes Endocrinol. 2018 May;6(5):361-369).
Behavioral: Intermittent fasting
The intermittent fasting intervention consists of a decreased daily caloric intake of 400 kcal below individual requirements (Harris Benedict Formula) combined with early time restricted fasting according to the schema 16:8. fasting will be performed over 4 weeks.

Behavioral: Control diet
Control group will be advised to reduce daily caloric intake of 400 kcal below individual requirements (Harris Benedict formula)




Primary Outcome Measures :
  1. Change in first phase insulin secretion. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effect of intermittent fasting vs. a control diet on glucose stimulated first phase insulin secretion adjusted for insulin sensitivity during an hyperglycemic clamp.


Secondary Outcome Measures :
  1. Change in second phase insulin secretion. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effect of intermittent fasting vs. a control diet on glucose stimulated second phase insulin secretion adjusted for insulin sensitivity during an hyperglycemic clamp.

  2. Change in insulin sensitivity. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effect of intermittent fasting vs. a control diet on insulin sensitivity using insulin sensitivity index during an hyperglycemic clamp.

  3. Change in BMI. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effect of intermittent vs. a control diet fasting on BMI.

  4. Change in liver fat content. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effects of intermittent fasting vs. a control diet on liver fat content (%) measured by magnetic resonance spectroscopy (3 T whole body imaging).

  5. Change in pancreatic fat content. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effects of intermittent fasting on pancreatic fat content (%) measured by magnetic resonance spectroscopy (3 T whole body imaging).

  6. Change in body fat content. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effects of intermittent fasting vs. a control diet on total adipose tissue (TAT) measured by magnetic resonance tomography (3 T whole body imaging).

  7. Change in visceral adipose tissue. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effects of intermittent fasting vs. a control diet on visceral adipose tissue (VAT) measured by by magnetic resonance tomography (3 T whole body imaging)

  8. Change in subcutaneous adipose tissue. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effects of intermittent fasting vs. a control diet on subcutaneous adipose tissue (SCAT) measured by by magnetic resonance tomography (3 T whole body imaging)


Other Outcome Measures:
  1. Change in brain insulin sensitivity. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effects of intermittent fasting vs. a control diet on brain insulin sensitivity measured by functional magnetic resonance imaging (fMRI) combined with nasal insulin administration.

  2. Change in resting energy expenditure (REE). [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effects of intermittent fasting vs. a control diet on resting energy expenditure measured by indirect calorimetry.

  3. Change in substrate oxidation. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effects of intermittent fasting vs. a control diet on substrate oxidation measured by indirect calorimetry.

  4. Change in proinsulin processing. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effect of intermittent fasting vs. a control diet on first phase proinsulin processing during an hyperglycemic clamp.

  5. Change in glucagon suppression. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effect of intermittent fasting vs. a control diet on glucagon suppression during an hyperglycemic clamp.

  6. Change in insuin clearance. [ Time Frame: Before, after 4 weeks and after 24 weeks of lifestyle intervention. ]
    Effect of intermittent fasting vs. a control diet on insulin clearance during an hyperglycemic clamp.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04607096


Contacts
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Contact: Andreas Fritsche, MD +49 7071 29 80590 andreas.fritsche@med.uni-tuebingen.de
Contact: Michael Roden, MD +49 211 3382 201 michael.roden@ddz.de

Locations
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Germany
Charité Berlin - Department of Endocrinology and Metabolic Diseases Not yet recruiting
Berlin, Germany, 10117
Contact: Joachim Spranger, MD    +49 30 450 514 252    joachim.spranger@charite.de   
Universtiy Hospital Carl Gustav Carus Not yet recruiting
Dresden, Germany, 01307
Contact: Peter Schwarz, MD    +49 (0) 351 458271    peter.schwarz@uniklinikum-dresden.de   
German Diabetes Center Not yet recruiting
Duesseldorf, Germany, 40225
Contact: Michael Roden, MD    +49 211 3382 201    michael.roden@ddz.de   
Heidelberg University Hospital - Department of Endocrinology and Metabolism Not yet recruiting
Heidelberg, Germany, 69120
Contact: Julia Szendrödi, MD    +49 (0) 6221 56-8601    Julia.Szendrödi@med.uni-heidelberg.de   
University Hospital Leipzig - Clinic for Endocrinology and Nephrology Not yet recruiting
Leipzig, Germany, 04103
Contact: Matthias Blüher, MD    +49 (0)341 - 97 13320    Matthias.blüher@medizin.uni-leipzig.de   
University of Luebeck - Institute of Endocrinology and Diabetes Not yet recruiting
Luebeck, Germany, 23538
Contact: Sebastian Schmid, MD       Sebastian.Schmid@uni-luebeck.de   
Technical University of Munich - Else Kroener-Fresenius-Center for Nutritional Medicine Not yet recruiting
Munich, Germany, 80992
Contact: Hans Hauner, MD    +49 (0) 8928924911    hans.hauner@tum.de   
University Hospital Tuebingen - Institute for Diabetes Research and Metabolic Diseases (IDM) Recruiting
Tuebingen, Germany, 72076
Contact: Andreas Fritsche, MD    +49 7071 29 80590    andreas.fritsche@med.uni-tuebingen.de   
Sponsors and Collaborators
University Hospital Tuebingen
German Institute of Human Nutrition
Charite University, Berlin, Germany
University Hospital Carl Gustav Carus
University of Leipzig
Ludwig-Maximilians - University of Munich
University Hospital Heidelberg
University of Luebeck
German Diabetes-Center, Leibniz-Institut in Düsseldorf
German Center for Diabetes Research
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Responsible Party: University Hospital Tuebingen
ClinicalTrials.gov Identifier: NCT04607096    
Other Study ID Numbers: 596/2020BO1
First Posted: October 28, 2020    Key Record Dates
Last Update Posted: December 9, 2021
Last Verified: December 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Prediabetic State
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases