The goal of this clinical trial is to investigate the efficacy of semaglutide on body weight, insulin dose requirements and improvements in glucose control and safety aspects in regards to risk of hypoglycemia and diabetic ketoacidosis for patients with established Type 1 Diabetes.
This is a multicentre, randomised, double-blinded, placebo-controlled and investigator-initiated trial aimed to investigate the efficacy of semaglutide in patients with Type 1 Diabetes. Patients from all included diabetes care centres will at routine visits be screened for eligibility for the trial and offered participation. If accepted, the patients will be randomised to one of two intervention arms and undergo a series of different examinations prior to start of the intervention. The two arms consist of treatment with subcutaneous semaglutide injections or subcutaneous injections with semaglutide placebo. The baseline examinations entail documentation of insulin doses, dietary patterns, diabetes distress and treatment satisfaction questionnaires, anthropoimetric data (height, weight and calculation of BMI, waist circumference, waist-hip-ratio), blood work (HbA1c, fasting glucose, fasting c-peptide, lipids, liver and kidney markers incl. Fib-4-scoring, hematology, hsCRP), ECG, capturing of data from continuous/flash glucose monitors. The first 40 included in the study from the centres of SDCA and NOH will further be examined through hyperinsulinemic euglycemic clamps to determine their insulin sensitivity and asses their transcriptome through muscle and fat cell biopsies in relation to the clamp and also be assessed through DXA scans to look at body composition and bone density. Patients will then be handed out their trial drug-pens and start the uptitration proces. The efficacy of semaglutide will be evaluated through the above mentioned array of different investigations by comparing parameters prior to trial drug start, during (throughout the study period), at the end of the drug and at a 6 week post-study followup in an intention-to-treat analysis primarily and secondarily a per-protocol analysis. The safety will be assessed through evaluation of standardized adverse event reporting (including hypoglycemic events and diabetic ketoacidosis).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
122
The active comparator of the intervention is s.c. Semaglutide injection once a week in increasing doses every month from 0.25 mg to 0.5 mg to 1.0 mg to 1.7 mg to 2.4 mg and the placebo comparator is s.c. injection with a visually identical and same label pen as described for the active comparator
Visually identical and same label as the active comparator intervention
Nordsjaellands Hospital
Hillerød, Denmark, Denmark
Body weight
Body weight will be measured both prior to and following treatment for 68 weeks with either semaglutide or placebo. Changes in body weight will be compared for the two intervention arms, before, throughout and at the end of treatment and then at followup 6 weeks later.
Time frame: 74 weeks
Systolic blood pressure
Systolic blood pressure will be assessed at randomization and evaluated for changes throughout, at the end of treatment and at followup 6 weeks later.
Time frame: 74 weeks
Diastolic blood pressure
Diastolic blood pressure will be assessed at randomization and evaluated for changes throughout, at the end of treatment and at followup 6 weeks later.
Time frame: 74 weeks
Resting heart rate
Systolic blood pressure will be assessed at randomization and evaluated for changes throughout, at the end of treatment and at followup 6 weeks later.
Time frame: 74 weeks
Waist circumference
Waist circumference will be assessed and evaluated for changes during and after treatment for 68 weeks with semaglutide compared to before treatment.
Time frame: 74 weeks
Hip-waist-ratio
Hip-waist-ratio will be assessed and evaluated for changes during and after treatment for 68 weeks with semaglutide compared to before treatment.
Time frame: 74 weeks
Hemoglobin
Blood samples will be analyzed to assess hemoglobin before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Leucocytes
Blood samples will be analyzed to assess leucocytes levels before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Thrombocytes
Blood samples will be analyzed to assess thrombocytes levels before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
HbA1c
Blood samples will be analyzed to assess HbA1c before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Fasting plasma-glucose
Blood samples will be analyzed to assess fasting plasma-glucose before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Fasting c-peptide
Blood samples will be analyzed to assess fasting c-peptide before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Total cholesterol
Blood samples will be analyzed to assess total cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
HDL cholesterol
Blood samples will be analyzed to assess HDL cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74
LDL cholesterol
Blood samples will be analyzed to assess LDL cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
VLDL cholesterol
Blood samples will be analyzed to assess VLDL cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Triglycerides
Blood samples will be analyzed to assess triglycerides levels before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
non-HDL cholesterol
Blood samples will be analyzed to assess non-HDL cholesterol before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Sodium
Blood samples will be analyzed to assess sodium before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Potassium
Blood samples will be analyzed to assess potassium before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Creatinine/eGFR
Blood samples will be analyzed to assess creatinine levels to calculate estimated Glomerular Filtration Rates (eGFR, based on sex, age and creatinine leve) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Alanine transaminase (ALT)
Blood samples will be analyzed to assess alanine transaminase (ALT) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Aspartate transaminase (AST)
Blood samples will be analyzed to assess aspartate transaminase (AST) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Fibrosis-4-score (Fib-4)
Blood samples will be analyzed for fibrosis-4-scores (based on age, thrombocytes, ALT and AST) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Amylase
Blood samples will be analyzed to assess pancreatic amylase before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Lipase
Blood samples will be analyzed to assess pancreatic lipase before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
High sensitivity C-reactive protein (hsCRP)
Blood samples will be analyzed to assess high sensitivity C-reactive protein (hsCRP) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Albumin
Blood samples will be analyzed to assess serum albumin before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up.
Time frame: 74 weeks
Ketones
Blood samples will be analyzed to assess total serum ketones before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up
Time frame: 74 weeks
CGM data - Time in range (TIR)
Data from CGMs will be analyzed to asses time in range (TIR) before treatment and evaluated for changes in TIR throughout the 68-week regimen and at its conclusion.
Time frame: 68 weeks
CGM data - Time in tight range (TITR)
Data from CGMs will be analyzed to asses time in tight range (TITR) before treatment and evaluated for changes in TITR throughout the 68-week regimen and at its conclusion.
Time frame: 68 weeks
CGM data - Time above range (TAR)
Data from CGMs will be analyzed to asses time above range (TAR) before treatment and evaluated for changes in TAR throughout the 68-week regimen and at its conclusion.
Time frame: 68 weeks
CGM data - Time below range (TBR)
Data from CGMs will be analyzed to asses time in range (TBR) before treatment and evaluated for changes in TBR throughout the 68-week regimen and at its conclusion.
Time frame: 68 weeks
CGM data - coefficient of variation (CV)
Data from CGMs will be analyzed to asses coefficient of variation (CV) before treatment and evaluated for changes in CV throughout the 68-week regimen and at its conclusion.
Time frame: 68 weeks
Total daily dose of insulin
Total daily dose will be assessed at randomization and evaluated for changes throughout treatment regimen, at the end of study and at six weeks followup through the use of insulin dose diaries.
Time frame: 74 weeks
Insulin sensitivity
For a subgroup consisting of the first 40 patients from two specified sites: Insulin sensitivity will be assessed through the golden standard hyperinsulinemic euglycemic clamping method. This will be done before treatment and at the end of treatment.
Time frame: 68 weeks
Fat percentage
For a subgroup consisting of the first 40 patients from two specified sites: The fat percentage is measured by DXA scan at randomisation and at end-of-treatment.
Time frame: 68 weeks
Lean mass
For a subgroup consisting of the first 40 patients from two specified sites: Lean body mass is measured by DXA scan at randomisation and at end-of-treatment.
Time frame: 68 weeks
Bone density (through bone mineral content)
For a subgroup consisting of the first 40 patients from two specified sites: Bone density (through bone mineral content) is measured by DXA scan at randomisation and at end-of-treatment.
Time frame: 68 weeks
Omics / Metabolome
For a subgroup consisting of the first 40 patients from two specified sites: Blood samples will be analyzed to assess metabolomic profile (entailing both lipidome and proteome) before treatment and evaluated for changes throughout the 68-week regimen, at its conclusion, and again six weeks post-treatment during follow-up
Time frame: 74 weeks
Muscle tissue biopsy
For a subgroup consisting of the first 40 patients from two specified sites: Muscle tissue biopsies will be taken to assess changes in transcriptome at randomisation and at end-of-treatment.
Time frame: 68 weeks
Fat tissue biopsy
For a subgroup consisting of the first 40 patients from two specified sites: Fat tissue biopsies will be taken to assess changes in transcriptome at randomisation and at end-of-treatment.
Time frame: 68 weeks
Electrocardiogram
Electrocardiograms (ECG) will be recorded at initiation and end of treatment period to assess and evaluate if any rhytm changes occur.
Time frame: 68 weeks
Thomas F Dejgaard, MD, ph.d., endocrinologist
CONTACT
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