The eHealth Diabetes Remission Trial (eDIT)

eHealth Diabetes Remission Trial (Swedish: Remission av Typ 2 Diabetes Med hjälp av eHälsa

Overweight patients with type 2 diabetes are offered a total diet replacement with the goal of weight loss and diabetes remission. Study participants are randomised to eHealth follow-up or face-to-face follow-up, but the dietary advice is the same in both groups. A healthy control group with normal glucose tolerance is examined once but is not randomised and does not receive any intervention.

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Behavioral: Total diet replacement; Behavioral: eHealth; Behavioral: Face-to-face

Detailed Description

One hundred and six overweight patients with type 2 diabetes replace usual foods with total diet replacement (850 kcal/day) for 3 months with the goal of 15 kg weight loss and diabetes remission (HbA1c < 48 mmol/mol without diabetes medication). After 3 months of total diet replacement, food is reintroduced stepwise, and an individually tailored energy prescription is used to prevent weight regain. If study participants do not reach the weight loss goal at 3 months, they are recommended two additional months of total diet replacement. If weight regain occurs during the weight maintenance phase, a rescue plan with total diet replacement will be recommended. To increase the chances to maintain their lower body weight, participants will use a program specifically design for that purpose based on cognitive behavioural therapy. Total study duration is two years.

The one hundred and six participants are randomised to either the eHealth follow-up or the face-to-face follow-up. The dietary advice to achieve and maintain weight loss is the same in both groups and delivered by the same dietician, physician, and nurse but the method of follow-up differs between groups (eHealth vs face-to-face).

eHealth group:

All study information and the cognitive behavioural therapy program is given by an eHealth application in Stöd och behandling which is part of 1177.se. Participants register body weight, fasting blood glucose, and blood pressure every morning at 1177.se. Regularly a measurement of HbA1c is taken at home. Participants will have scheduled video appointments with the study dietician, study nurse or study physician.

Face-to-face group:

Participants have appointments in the medical office with the study physician/nurse/dietician. At the appointments, body weight, blood pressure and capillary blood glucose is measured. HbA1c is measured during the appointments at 0, 6, 12 and 24 months. The cognitive behavioral therapy program for the control group is identical to the program of the intervention group, but the program is delivered during the face-to-face appointments.

Healthy control group:

Fifteen healthy participants with normal glucose tolerance, stable body weight for at least one year and matched to the study participants for sex, age, and weight after one year study duration, will be examined once. These participants are not randomised and do not receive any intervention.

Outcomes:

Primary and secondary outcome measures are compared between 1) the experimental eHealth group and 2) the experimental face-to-face group. For the other pre-specified outcome measures the experimental eHealth group and the experimental face-to-face group are taken together as one group, examined twice (baseline and 12 months) and compared to the healthy control group, that is examined only once.

Long-term follow-up:

Because long term data on diabetes remission by total diet replacement are lacking, study participants will be followed after they have finished the study. Data of the national diabetes registry from participants of this study will be compared to other patients in the national diabetes registry not participating in this study but matched for age, sex and diabetes duration to the study participants.

• Study Type: Interventional
• Enrollment (Estimated): 106
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julia Otten, PhD; Phone Number: +46703341559; Email: julia.otten@umu.se

Study Locations

• Sweden
  • Jönköping, Sweden
    • Recruiting
    • Bra Liv Råslätt vårdcentral
    • Contact: Andreas Stomby, PhD
  • Umeå, Sweden, 90187
    • Recruiting
    • Department of Public Health and Clinical Medicine, Medicine
    • Contact: Julia Otten, MD, PhD
    • Principal Investigator: Julia Otten, MD, PhD
  • Örnsköldsvik, Sweden
    • Not yet recruiting
    • Örnsköldsvik hospital
    • Contact: Katarina Shahedi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Type 2 diabetes with duration 0-6 years
• BMI 27 kg/m2 and higher
• HbA1c 43 mmol/mol or higher (48 or higher if without diabetes medication)

Exclusion Criteria:

• Insulin treatment
• Weight loss more than 5 kg during the past 6 months
• Diagnosed eating disorder
• eGFR < 30 ml/min/1,73m2
• Myocardial infarction last six months
• Severe heart failure (NYHA class III)
• Ongoing cancer
• Pregnancy
• Treatment with antipsychotic drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: eHealth	Behavioral: Total diet replacement; Total diet replacement (850 kcal/day) for 3 months followed by weight maintenance for 21 months.; Behavioral: eHealth; All follow-up through an eHealth application and video meetings.
Experimental: Face-to-face	Behavioral: Total diet replacement; Total diet replacement (850 kcal/day) for 3 months followed by weight maintenance for 21 months.; Behavioral: Face-to-face; All follow-up through face-to-face meetings.
No Intervention: Healthy control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	HbA1c without diabetes medication as a continuous outcome (HbA1c correction according to Tsapas et al 2020 if on diabetes medication). The outcome will be tested for non-inferiority first, with a non-inferiority margin of 8 mmol/mol; followed by a test for superiority.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	HbA1c without diabetes medication as a continuous outcome (HbA1c correction according to Tsapas et al 2020 if on diabetes medication). The outcome will be tested for non-inferiority first, with a non-inferiority margin of 8 mmol/mol; followed by a test for superiority.	6 and 24 months
Diabetes remission	Number of participants with HbA1c < 48 mmol/mol without diabetes medication. The outcome will be tested for non-inferiority first with a non-inferiority margin of 10 percentage points; followed by a test for superiority.	6, 12 and 24 months
Body weight	Body weight as a continuous outcome	6, 12 and 24 months
Achieved weight loss of at least 15 kg	Number of participants with achieved weight loss of at least 15 kg	6, 12 and 24 months
Incremental costs per diabetes remission		24 months
Estimated lifetime costs		24 months
Estimated lifetime costs per quality-adjusted life-year (QALY)		24 months
Fasting blood glucose	Partial diabetes remission (<7.0 mol/l), complete diabetes remission (<6.1 mol/l) without diabetes medication.	6, 12, 24 months
P-glucose 120 minutes after the oral glucose tolerance test		6, 12, 24 months
Number of prescribed oral anti diabetic medications		6, 12, 24 months
Number of prescribed antihypertensive medications		6, 12, 24 months
Blood pressure (systolic/diastolic)	Measured at the research facilities	6, 12, 24 months
Blood pressure	24h monitoring	6, 12, 24 months
Plasma lipid profile		6, 12, 24 months
Liver enzymes	AST, ALT	6, 12, 24 months
Number of participants that discontinue the intervention		6, 12, 24 months
Waist circumference		6, 12, 24 months
Relation to food	Three factor eating questionnaire	6, 12, 24 months
Estimation of exhaustion	Karolinska Exhaustion Disorder Scale. Minimum value 0. Maximum value 54. A higher score means a worse outcome.	6, 12, 24 months
Quality of life accoring to Brunnsviken Brief Quality of Life Scale	The scale estimates how satisfied the participants is with different areas of life, as well as how important each area of life is. Minimum scale 0. Maximum scale 48. A higher score means a better outcome.	6, 12, 24 months
Quality of life according to EQ-5D-5L	The questionnaire investigates the dimensions mobility, self-care, usual activities, pain and anxiety/depression. Minimum value 1. Maximum value 5. A higher score means a worse outcome. In addition, a general health score is assessed. Minimum value 0. Maximum value 100. A higher score means a better outcome. All dimension will be analysed separately, but EQ-5D-5L will also be combined to one score.	6, 12, 24 months
Eating habits	FFQ 2020 questionnaire	6, 12, 24 months
Estimation of health	SF-36 questionnaire	6, 12, 24 months
Daily steps	Measured with activity tracker	6, 12, 24 months
Study experience	Qualitative questions with written answers about study experience	24 months
HbA1c follow-up	Collected from patient journals after study completion	Yearly up to 20 years
Body weight follow-up	Collected from patient journals after study completion	Yearly up to 20 years
Blood pressure follow-up	Collected from patient journals after study completion	Yearly up to 20 years
Usage of diabetes medication follow-up	Collected from patient journals after study completion	Yearly up to 20 years
Usage of hypertension medication follow-up	Collected from patient journals after study completion	Yearly up to 20 years
Diabetes complications follow-up	Collected from patient journals and registries after study completion	Yearly up to 20 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity	Hyperinsulinemic euglycemic clamp	12 months
Insulin secretion	Stepped insulin secretion test with arginine	12 months
Metabolic flexibility	Hyperinsulinemic euglycemic clamp	12 months
Resting metabolic rate	Indirect calorimetry	12 months
Body composition	Dual-energy X-ray absorptiometry (DXA).	12 months
Glucagon sensitivity	Plasma amino acids are measured during 120 minutes after a intravenous glucagon bolus	12 months
Amino acid tolerance	Plasma amino acids are measured during intravenous amino acid infusion	12 months
Glucagon secretion capacity	Plasma glucagon is measured during intravenous amino acid infusion	12 months
Gut hormones after carbohydrate intake	GLP-1, GIP and gherkin during the oral glucose tolerance test	6, 12, 24 months
P-metabolites and P-lipids after carbohydrate intake	Metabolomics and lipidomics analyses during the oral glucose tolerance test	6, 12, 24 months
Liver fat	Measured with MRI	12 months
Pancreas fat	Measured with MRI	12 months
Fat cell size in subcutaneous fat		12 months
RNA levels in subcutaneous fat	RNA sequencing	12 months
Secretion of adipokines, metabolites and lipids in subcutaneous fat cells ex vivo		12 months
Plasma testosterone levels	Only men	6, 12 and 24 months
Erectile function	Only men, Erectile function subscale	6, 12, 24 months
Prostate symptoms	Only men, International prostate symptom score	6, 12, 24 months
Urine albumin to creatinine ratio		6, 12, 24 months
Slow vital capacity (SVC)	Spirometry	12 months
Forced vital capacity (FVC)	Spirometry	12 months
Forced expiratory volume in 1 s (FEV1)	Spirometry	12 months
Diffusion capacity of the the (DCLO)	Spirometry	12 months
Troponin T		6, 12 and 24 months
proBNP		6, 12 and 24 months

Collaborators and Investigators

• Sponsor: Umeå University
• Collaborators: Region Västerbotten; Edgar Sjölunds Diabetes Foundation
• Investigators: Principal Investigator: Julia Otten, PhD, Umeå University

Publications and helpful links

General Publications

• Tsapas A, Avgerinos I, Karagiannis T, Malandris K, Manolopoulos A, Andreadis P, Liakos A, Matthews DR, Bekiari E. Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2020 Aug 18;173(4):278-286. doi: 10.7326/M20-0864. Epub 2020 Jun 30.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: August 3, 2022
• First Submitted That Met QC Criteria: August 5, 2022
• First Posted (Actual): August 8, 2022

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Obesity; Weight Loss; eHealth; Diabetes Remission; Nutrition Therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: Dnr 2022-02242-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be shared with other researchers on reasonable request.
• IPD Sharing Time Frame: Data is available to other researchers as soon as it is published.
• IPD Sharing Access Criteria: Data will be shared with other researchers on reasonable request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No