Clinical trial NCT01836523: The Efficacy and Safety of Liraglutide as Adjunct Therapy to Insulin in the Treatment of Type 1 Diabetes
Official title: The Efficacy and Safety of Liraglutide as Adjunct Therapy to Insulin in the Treatment of Type 1 Diabetes. A 52-week Randomised, Treat-to-target, Placebo-controlled, Double Blinded, Parallel Group, Multinational, Multi-centre Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 1
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2013-04-22
Enrollment: 1398
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted globally. The aim of the trial is to confirm the efficacy and safety of liraglutide as adjunct therapy to insulin in the treatment of type 1 diabetes. The total trial duration per subject is approximately 58 weeks.


Eligibility criteria: Inclusion Criteria:

* - Informed consent obtained
* - Type 1 diabetes mellitus for 12 months or longer
* - Basal bolus or CSII (Continuous Subcutaneous Insulin Infusion, insulin pump) treatment for 6 months or longer
* - Stable insulin treatment for the last 3 months prior to Screening, as judged and documented by the investigator
* - HbA1c 7.0-10% (Diabetes Control and Complications Trial (DCCT)), both inclusive, (corresponding to 53-86 mmol/mol (International Federation of Clinical Chemistry (IFCC))
* - Ability and willingness to comply with all protocol procedures e.g. correct handling of trial product, complete trial related questionnaires, diaries, self-monitoring of plasma glucose, self titration of insulin and attend all scheduled visits

Exclusion Criteria:

* - Prior use of glucagon-like peptide-1 (GLP-1) receptor agonist or dipeptidyl peptidase IV (DPP-4) inhibitors
* - Use of any medication, which in the investigator's opinion could interfere with the glycaemic control or affect the subject's safety.Premix insulin is not allowed
* - Known proliferative retinopathy or maculopathy requiring acute treatment
* - Severe neuropathy, in particular autonomic neuropathy, i.e. gastroparesis, as judged by the investigator
* - Uncontrolled/ untreated blood pressure at screening above 160 mmHg for systolic or above 100 mmHg for diastolic
* - History of acute or chronic pancreatitis
* - Screening calcitonin value equal to or above 50 ng/L
* - Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia type 2 (MEN2)
* - Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)

Primary outcomes:
measure: Change From Baseline in HbA1c (Glycosylated Haemoglobin)
timeFrame: Week 0, week 52
measure: Change From Baseline in Body Weight
timeFrame: Week 0, week 52
measure: Change From Baseline in Total Daily Insulin Dose
timeFrame: Week 0, week 52
Secondary outcomes:
measure: Number of Treatment-emergent Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-52
Other outcomes:
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country: United States
facility: Novo Nordisk Investigational Site
state: Arkansas
city: Concord
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Encino
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state: California
city: Escondido
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city: Huntington Beach
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city: Chattanooga
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city: Chattanooga
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city: Memphis
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city: Nashville
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city: Nashville
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city: Amarillo
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city: Dallas
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state: Texas
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state: Texas
city: Dallas
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state: Texas
city: El Paso
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city: Round Rock
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city: Salt Lake City
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city: Bennington
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city: Norfolk
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city: Lublin
country: Poland
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city: Pulawy
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city: Warszawa
country: Poland
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city: Warszawa
country: Poland
facility: Novo Nordisk Investigational Site
city: Zabrze
country: Poland
facility: Novo Nordisk Investigational Site
city: Kazan
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Kazan
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Penza
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Volgograd
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Göteborg
country: Sweden
facility: Novo Nordisk Investigational Site
city: Malmö
country: Sweden
facility: Novo Nordisk Investigational Site
city: Stockholm
country: Sweden
facility: Novo Nordisk Investigational Site
city: Stockholm
country: Sweden
facility: Novo Nordisk Investigational Site
city: Kharkov
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Kharkov
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Kiev
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Poltava
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Zhytomir
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Blackburn
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bristol
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Durham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Edgbaston, Birmingham
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Edinburgh
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Middlesbrough
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Plymouth
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Southall
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: St Helens
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Stevenage
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Mathieu C, Zinman B, Hemmingsson JU, Woo V, Colman P, Christiansen E, Linder M, Bode B; ADJUNCT ONE Investigators. Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial. Diabetes Care. 2016 Oct;39(10):1702-10. doi: 10.2337/dc16-0691. Epub 2016 Aug 9.
citation: Dejgaard TF, von Scholten BJ, Christiansen E, Kreiner FF, Bardtrum L, von Herrath M, Mathieu C, Madsbad S; ADJUNCT ONE and ADJUNCT TWO Investigators. Efficacy and safety of liraglutide in type 1 diabetes by baseline characteristics in the ADJUNCT ONE and ADJUNCT TWO randomized controlled trials. Diabetes Obes Metab. 2021 Dec;23(12):2752-2762. doi: 10.1111/dom.14532. Epub 2021 Sep 28.