Clinical trial NCT02092896: Liraglutide as add-on to Insulin in Type 1 Diabetes
Official title: Treatment With Liraglutide as add-on to Insulin in Type 1 Diabetic Patients. Effects on Glycemic Control and Counterregulation and Cognitive Performance During Hypoglycaemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 1
Keywords: Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Cognitive performance
Hypoglycemia
Insulin
Glucagon-Like Peptide 1
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Incretins
Hormones
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
Collaborators: name: NNF Center for Basal Metabolic Research, Denmark
name: Hillerod Hospital, Denmark
name: Danish PhD schools of Molecular Metabolism and Endocrinology
name: Novo Nordisk A/S
First posted: 2014-03-20
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to:

Part 1:

To investigate how 12 weeks treatment with liraglutide affects glycemic control in poorly controlled patients and how the treatment affects gastric emptying rate during hypoglycemia.

Part 2:

To investigate how 12 weeks treatment of type 1 diabetic patients with liraglutide affects counterregulatory hormones and cognitive performance during hypoglycemia.


Eligibility criteria: Inclusion Criteria:

* Age: 18-70 years
* BMI: 18-28
* HbA1c ≥ 8 %
* No residual β-cell function (glucagon test with c-peptide \< 60 pM)
* Caucasian
* Diagnosed with type 1 diabetes at 5 to 40 years of age (both inclusive).
* Remission phase must be completed
* Female participants must use adequate contraception
* Informed consent

Exclusion Criteria:

* Overt diabetes complications; creatinin \> 130 µM, proliferative retinopathy, macroalbuminuria.
* Autonomic neuropathy (RR-variation \</=10 beats/min) and/or Orthostatic hypotension (OH).
* Anemia, Hb concentration; female \<7.0 mmol/l, male\<8.0 mmol/l
* Pregnancy or lactation
* Epilepsy
* Use of antiepileptic medication
* Use of beta blockers
* Previously apoplexy cerebri.
* Any use of benzodiazepine within the last month
* Any use of neuroleptic drugs within the last six months
* Self-perceived hearing loss
* Alcohol or drug abuse
* Allergy to the medication or placebo.
* Treatment with any medication affecting glucose metabolism.
* Any disorder which in the investigators opinion could interfere with the safety and results of the trial

Primary outcomes:
measure: Change from baseline in HbA1c (glycosylated haemoglobin)
timeFrame: Week 0, week 12
measure: Changes from baseline in EEG and cognitive performances
timeFrame: week 0, week 12
measure: Change from baseline in gastric emptying rate
timeFrame: week 0, week 12
Secondary outcomes:
measure: Change from baseline in glycemic control (CGM)
timeFrame: week 0, week 12
measure: Change from baseline in total daily insulin dose
timeFrame: week 0, week 12
measure: Changes from baseline in the counterregulatory hormone responses during hypoglycemia
timeFrame: week 0, week 12
measure: Change from baseline in body weight
timeFrame: week 0, week 12
measure: Change from baseline in auditory evoked potentials (AEP) during hypoglycemia
timeFrame: week 0, week 12
measure: Change from baseline in corrected QTc-interval (QTc) during hypoglycemia
timeFrame: week 0, week 12
measure: Change from baseline in hypoglycemic symptom score
timeFrame: week 0, week 12
Other outcomes:
measure: Frequency of Hypoglycemic episodes
timeFrame: Week 0, week 12
Locations:
city: Hvidovre
country: Denmark
facility: Dept. of Endocrinology, Hvidovre University Hospital
state: Copenhagen
Study officials:
affiliation: Hvidovre University Hospital
name: Christian SS Frandsen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Frandsen CS, Dejgaard TF, Holst JJ, Andersen HU, Thorsteinsson B, Madsbad S. Twelve-Week Treatment With Liraglutide as Add-on to Insulin in Normal-Weight Patients With Poorly Controlled Type 1 Diabetes: A Randomized, Placebo-Controlled, Double-Blind Parallel Study. Diabetes Care. 2015 Dec;38(12):2250-7. doi: 10.2337/dc15-1037. Epub 2015 Oct 20.