NCT04607096

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
200

participants targeted

Target at P75+ for not_applicable

Timeline
10mo left

Started Apr 2021

Longer than P75 for not_applicable

Geographic Reach
1 country

8 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress86%
Apr 2021Mar 2027

First Submitted

Initial submission to the registry

October 22, 2020

Completed
6 days until next milestone

First Posted

Study publicly available on registry

October 28, 2020

Completed
5 months until next milestone

Study Start

First participant enrolled

April 8, 2021

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2027

Last Updated

April 21, 2026

Status Verified

April 1, 2026

Enrollment Period

5.7 years

First QC Date

October 22, 2020

Last Update Submit

April 20, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Change in first phase insulin secretion.

    Effect of intermittent fasting vs. a control diet on glucose stimulated first phase insulin secretion adjusted for insulin sensitivity during an hyperglycemic clamp.

    Before, after 4 weeks and after 24 weeks of lifestyle intervention.

Secondary Outcomes (8)

  • Change in second phase insulin secretion.

    Before, after 4 weeks and after 24 weeks of lifestyle intervention.

  • Change in insulin sensitivity.

    Before, after 4 weeks and after 24 weeks of lifestyle intervention.

  • Change in BMI.

    Before, after 4 weeks and after 24 weeks of lifestyle intervention.

  • Change in liver fat content.

    Before, after 4 weeks and after 24 weeks of lifestyle intervention.

  • Change in pancreatic fat content.

    Before, after 4 weeks and after 24 weeks of lifestyle intervention.

  • +3 more secondary outcomes

Other Outcomes (6)

  • Change in brain insulin sensitivity.

    Before, after 4 weeks and after 24 weeks of lifestyle intervention.

  • Change in resting energy expenditure (REE).

    Before, after 4 weeks and after 24 weeks of lifestyle intervention.

  • Change in substrate oxidation.

    Before, after 4 weeks and after 24 weeks of lifestyle intervention.

  • +3 more other outcomes

Study Arms (4)

Prediabetic subjects - cluster 3

ACTIVE COMPARATOR

Presence of a cluster 3 phenotype will be examined according to the parameters described by Wagner et al.(Nat. Med. 2020).

Behavioral: Intermittent fastingBehavioral: Control diet

Prediabetic subjects - cluster 5

ACTIVE COMPARATOR

Presence of a cluster 5 phenotype will be examined according to the parameters described by Wagner et al.(Nat. Med. 2020).

Behavioral: Intermittent fastingBehavioral: Control diet

Patients with type 2 diabetes - subphenotype: Severe insulin-deficient diabetes (SIDD)

ACTIVE COMPARATOR

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 fastingBehavioral: Control diet

Patients with type 2 diabetes - subphenotype: Severe insulin-resistant diabetes (SIRD)

ACTIVE COMPARATOR

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).

Interventions

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.

Patients with type 2 diabetes - subphenotype: Severe insulin-deficient diabetes (SIDD)Prediabetic subjects - cluster 3Prediabetic subjects - cluster 5
Control dietBEHAVIORAL

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

Patients with type 2 diabetes - subphenotype: Severe insulin-deficient diabetes (SIDD)Prediabetic subjects - cluster 3Prediabetic subjects - cluster 5

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 type 2 diabetes mellitus (diagnosed \<5 years prior to screening), HbA1c 6.0% - 9.5%, not receiving insulin or thiazolidinediones, and with an appropriate washout period for all other antidiabetic medications)

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Charité Berlin - Department of Endocrinology and Metabolic Diseases

Berlin, 10117, Germany

RECRUITING

Universtiy Hospital Carl Gustav Carus

Dresden, 01307, Germany

RECRUITING

German Diabetes Center

Düsseldorf, 40225, Germany

RECRUITING

Heidelberg University Hospital - Department of Endocrinology and Metabolism

Heidelberg, 69120, Germany

RECRUITING

University Hospital Leipzig - Clinic for Endocrinology and Nephrology

Leipzig, 04103, Germany

RECRUITING

University of Luebeck - Institute of Endocrinology and Diabetes

Lübeck, 23538, Germany

RECRUITING

Technical University of Munich - Else Kroener-Fresenius-Center for Nutritional Medicine

Munich, 80992, Germany

RECRUITING

University Hospital Tuebingen - Institute for Diabetes Research and Metabolic Diseases (IDM)

Tübingen, 72076, Germany

RECRUITING

Related Publications (1)

  • Heilmann G, Trenkamp S, Moser C, Bombrich M, Schon M, Yurchenko I, Strassburger K, Rodriguez MM, Zaharia OP, Burkart V, Wagner R, Roden M. Precise glucose measurement in sodium fluoride-citrate plasma affects estimates of prevalence in diabetes and prediabetes. Clin Chem Lab Med. 2023 Oct 24;62(4):762-769. doi: 10.1515/cclm-2023-0770. Print 2024 Mar 25.

MeSH Terms

Conditions

Prediabetic StateIntermittent Fasting

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesFastingFeeding BehaviorBehavior

Central Study Contacts

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Participants wil either receive a control diet or join the intermittent fasting group stratified by glycemia (prediabetes/diabetes) as well as by subphenotype.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 22, 2020

First Posted

October 28, 2020

Study Start

April 8, 2021

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

March 1, 2027

Last Updated

April 21, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations