Type 2 Diabetes MellitusPhase 4NCT01638260
GLP-1 and Non-exercise Activity Thermogenesis in RHZ
A Phase 4 study testing Liraglutide and NEAT in people with Type 2 Diabetes Mellitus, run by Maastricht University Medical Center at 1 site in Netherlands.
Trial summary
Rationale: Treatment with glucagon-like peptide 1 (GLP-1) has been shown to reduce plasma glucose levels to a further extent when added to standard therapy in type 2 diabetes mellitus. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Liraglutide and NEAT
- Type of treatment
- Injection or infusion, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2012to Nov 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent obtained before any study-related activities
- Men or women with type 2 diabetes mellitus
- Insufficiënt glycaemic control during maximum (tolerable) dose monotherapy with metformin or a sulfonylurea derivate or during combination therapy with metformin and a sulfonylurea derivate or a thiazolinedione
- HbA1c ≥ 7.0% at screening
- BMI ≥ 25.0 kg/m2 at screening
- Age between 40-75 years
Who cannot join
- Type 1 diabetes mellitus
- HbA1c ≥ 10% at screening
- Use of GLP-1 receptor agonist (exenatide, liraglutide or other) or pramlintide or any DDP-4 inhibitor within 3 months prior to screening
- Use of insulin within 3 months prior to screening
- An acute coronary or cerebrovascular event in the previous 3 months at screening
- Chronic heart failure NYHA class IV at screening
Show all 17Show fewer
- Estimated glomerular filtration rate (eGFR) as per Modification of Diet in Renal Disease (MDRD) < 30 ml/min/1.73m2 at screening
- Liver disease, defined as alanine or aspartate aminotransferase levels more than 2.5 the upper limit of normal range at screening
- Malignant neoplasm
- Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or family history of medullary thyroid cancer
- Chronic or acute pancreatitis
- Abuse or dependence of alcohol or drugs (as defined by DSM-IV)
- Any acute condition or exacerbation of chronic condition that would in the investigator's opinion interfere with the study
- Known or suspected hypersensitivity or intolerance to liraglutide
- Known to be uncooperative or noncompliant
- Simultaneous participation in any other clinical study of an investigational product
- Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Liraglutide With or Without NEAT in Type 2 Diabetes Mellitus; Effects on HbA1c, Weight, Blood Pressure, Quality of Life and Health Care Costs.
- Rationale: Treatment with glucagon-like peptide 1 (GLP-1) has been shown to reduce plasma glucose levels to a further extent when added to standard therapy in type 2 diabetes mellitus. Given the well-known beneficial effects of GLP-1 analogues on glucose metabolism by stimulating insulin release, suppressing elevated glucagon levels, delaying gastric emptying and reducing food intake, it is anticipated that liraglutide developed by Novo Nordisk (Victoza®) also has beneficial effects in type 2 diabetes mellitus as has been proven by several trials. Type 2 diabetes mellitus is associated with obesity and sedentary lifestyle. Obesity occurs when energy intake exceeds energy expenditure (EE) over a period of time. It has been presumed that activity energy expenditure and daily energy expenditure are lower in most people in Western societies. Increasing non-exercise activity thermogenesis (NEAT), defined as all energy expended due to everyday activity, exclusive of volitional exercise, may be an effective way to maintain daily EE and combat overweight and obesity. One way to promote NEAT is to decrease the amount of time spent on sedentary behaviors (e.g. watching television).
This leads us to hypothesize that adding NEAT to GLP-1 analogues in type 2 diabetes has an additive effect on glucose regulation, weight control and blood pressure. On the other hand, we hypothesize that a decrease in HbA1c, weight and blood pressure could add to an improved quality of life and less health care costs. Therefore, the primary purpose of this study is to determine the synergistic effect of liraglutide and activating lifestyle by increasing NEAT on glucose metabolism and weight. First line therapy of type 2 diabetes mellitus currently consists of lifestyle changes with metformin. When failure of this regime occurs, sulfonylurea derivates and/or thiazolidinediones can be added. One third of patients with type 2 diabetes mellitus fail with this regimen after 5 years of monotherapy, and nowadays GLP-1 analogues can be added to prevent deterioration of glycaemic control. However, comparison of this strategy with NEAT has not been performed and the synergistic effect of combination of GLP-1 with increasing NEAT has not been investigated. Treatment with GLP-1 analogues in combination with NEAT could theoretically overcome all shortcomings of current treatment strategies of type 2 diabetes mellitus.
Read more
Objective:
- Primary objectives
- To determine the change in HbA1c from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- To determine the change in weight from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- Secondary objectives
- To assess the change in blood pressure from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- To assess the change in quality of life from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- To assess the change in NEAT from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- To asses the health-care related costs at baseline, after 26 weeks of treatment with liraglutide versus liraglutide with NEAT, and after 52 weeks (end of follow-up)
Study design: Randomized controlled intervention study
- Study population: Men and women with type 2 diabetes mellitus, insufficiënt glycaemic control during maximum (tolerable) dose monotherapy with metformin or a sulfonylurea derivate or during combination therapy with metformin and a sulfonylurea derivate or a thiazolinedione, HbA1c above 7,0%, age between 40 - 75 years old, BMI above 25 kg/m2
Intervention: One group receives once daily subcutaneously liraglutide 1.8mg added to standard anti-diabetic care and the other group receives once daily subcutaneously liraglutide 1.8mg added to standard anti-diabetic care and an activating lifestyle by increasing NEAT
Main study parameters/endpoints: The main study parameter is the percent change in HbA1c and weight. Secondary study parameters are change in blood pressure, quality of life as measured using EQ-5D and SF-36 questionnaire, NEAT as measured using an activPAL™ accelerometer and cost-effectiveness analysis.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Liraglutide, NEAT
- Keywords
- NEAT, liraglutide, glycemic control
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Liraglutide once daily 1.8 mg injection subcutaneously, 26 weeks
NEATBehavioural
Increasing NEAT by activating lifestyle interventions, combined with liraglutide once daily 1.8mg injections subcutaneously
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide | Placebo comparator | Subjects will inject liraglutide once daily for 26 weeks Receives: Drug: Liraglutide |
| Liraglutide and NEAT | Active comparator | Subjects will inject liraglutide once daily and combine this treatment with activating lifestyle, by increasing NEAT. Receives: Behavioral: NEAT |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in HbA1c from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Measured: 6 times, screening, week 0, week 13-26-39-52
Change in weight from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Measured: 6 times, screening, week 0, week 13-26-39-52
Secondary outcomes (4)
Change in blood pressure from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Measured: 6 times, screening, week 0, week 13-26-39-52
Change in quality of life from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Quality of life questionnaires SF-36 en EQ-5D will be used.
Measured: 3 times, week 0, 26, 52
Change in NEAT from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Neat will be measured using ActivPal accelerometer during one week.
Measured: 3 times, week 0, 26, 52
Health-care related costs
Measured: At baseline, after 26 weeks and after 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2012 (estimated)
- Study startOct 2012
- Primary completionNov 2013
- Study completionNov 2013
Why it stopped: Terminated because of insufficient number of subjects included.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Maastricht University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolaas C Schaper, Prof., MD, Principal investigator, Maastricht University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01638260
- Sponsor's protocol ID
- METC 12-2-033
- Status last verified
- Dec 2013
- First submitted
- 9 Jul 2012
- Last updated
- 17 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liraglutide With or Without NEAT in Type 2 Diabetes Mellitus; Effects on HbA1c, Weight, Blood Pressure, Quality of Life and Health Care Costs.
- ClinicalTrials.gov ID
- NCT01638260
- Acronym / sponsor ID
- METC 12-2-033
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- NEAT, liraglutide, glycemic control
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Terminated because of insufficient number of subjects included.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Maastricht University Medical CenterUniversity, hospital or other
- Study start
- Oct 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 11 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- Rationale: Treatment with glucagon-like peptide 1 (GLP-1) has been shown to reduce plasma glucose levels to a further extent when added to standard therapy in type 2 diabetes mellitus. Given the well-known beneficial effects of GLP-1 analogues on glucose metabolism by stimulating insulin release, suppressing elevated glucagon levels, delaying gastric emptying and reducing food intake, it is anticipated that liraglutide developed by Novo Nordisk (Victoza®) also has beneficial effects in type 2 diabetes mellitus as has been proven by several trials. Type 2 diabetes mellitus is associated with obesity and sedentary lifestyle. Obesity occurs when energy intake exceeds energy expenditure (EE) over a period of time. It has been presumed that activity energy expenditure and daily energy expenditure are lower in most people in Western societies. Increasing non-exercise activity thermogenesis (NEAT), defined as all energy expended due to everyday activity, exclusive of volitional exercise, may be an effective way to maintain daily EE and combat overweight and obesity. One way to promote NEAT is to decrease the amount of time spent on sedentary behaviors (e.g. watching television).
This leads us to hypothesize that adding NEAT to GLP-1 analogues in type 2 diabetes has an additive effect on glucose regulation, weight control and blood pressure. On the other hand, we hypothesize that a decrease in HbA1c, weight and blood pressure could add to an improved quality of life and less health care costs. Therefore, the primary purpose of this study is to determine the synergistic effect of liraglutide and activating lifestyle by increasing NEAT on glucose metabolism and weight. First line therapy of type 2 diabetes mellitus currently consists of lifestyle changes with metformin. When failure of this regime occurs, sulfonylurea derivates and/or thiazolidinediones can be added. One third of patients with type 2 diabetes mellitus fail with this regimen after 5 years of monotherapy, and nowadays GLP-1 analogues can be added to prevent deterioration of glycaemic control. However, comparison of this strategy with NEAT has not been performed and the synergistic effect of combination of GLP-1 with increasing NEAT has not been investigated. Treatment with GLP-1 analogues in combination with NEAT could theoretically overcome all shortcomings of current treatment strategies of type 2 diabetes mellitus.
Objective:
- Primary objectives
- To determine the change in HbA1c from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- To determine the change in weight from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- Secondary objectives
- To assess the change in blood pressure from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- To assess the change in quality of life from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- To assess the change in NEAT from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) after 26 weeks of treatment with liraglutide versus liraglutide with NEAT
- To asses the health-care related costs at baseline, after 26 weeks of treatment with liraglutide versus liraglutide with NEAT, and after 52 weeks (end of follow-up)
Study design: Randomized controlled intervention study
- Study population: Men and women with type 2 diabetes mellitus, insufficiënt glycaemic control during maximum (tolerable) dose monotherapy with metformin or a sulfonylurea derivate or during combination therapy with metformin and a sulfonylurea derivate or a thiazolinedione, HbA1c above 7,0%, age between 40 - 75 years old, BMI above 25 kg/m2
Intervention: One group receives once daily subcutaneously liraglutide 1.8mg added to standard anti-diabetic care and the other group receives once daily subcutaneously liraglutide 1.8mg added to standard anti-diabetic care and an activating lifestyle by increasing NEAT
Main study parameters/endpoints: The main study parameter is the percent change in HbA1c and weight. Secondary study parameters are change in blood pressure, quality of life as measured using EQ-5D and SF-36 questionnaire, NEAT as measured using an activPAL™ accelerometer and cost-effectiveness analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liraglutide | Placebo comparator | Drug: LiraglutideSubjects will inject liraglutide once daily for 26 weeks |
| Liraglutide and NEAT | Active comparator | Behavioral: NEATSubjects will inject liraglutide once daily and combine this treatment with activating lifestyle, by increasing NEAT. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Informed consent obtained before any study-related activities
- Men or women with type 2 diabetes mellitus
- Insufficiënt glycaemic control during maximum (tolerable) dose monotherapy with metformin or a sulfonylurea derivate or during combination therapy with metformin and a sulfonylurea derivate or a thiazolinedione
- HbA1c ≥ 7.0% at screening
- BMI ≥ 25.0 kg/m2 at screening
Key exclusion criteria (17 listed)
- Type 1 diabetes mellitus
- HbA1c ≥ 10% at screening
- Use of GLP-1 receptor agonist (exenatide, liraglutide or other) or pramlintide or any DDP-4 inhibitor within 3 months prior to screening
- Use of insulin within 3 months prior to screening
- An acute coronary or cerebrovascular event in the previous 3 months at screening
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LiraglutideLiraglutide once daily 1.8 mg injection subcutaneously, 26 weeks | Drug | Liraglutide |
| NEATIncreasing NEAT by activating lifestyle interventions, combined with liraglutide once daily 1.8mg injections subcutaneously | Behavioural | Liraglutide and NEAT |
Primary outcome
Change in HbA1c from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Time frame: 6 times, screening, week 0, week 13-26-39-52
Change in weight from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Time frame: 6 times, screening, week 0, week 13-26-39-52
4 secondary outcomes
Change in blood pressure from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Time frame: 6 times, screening, week 0, week 13-26-39-52
Change in quality of life from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Time frame: 3 times, week 0, 26, 52
Change in NEAT from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks)
Time frame: 3 times, week 0, 26, 52
Health-care related costs
Time frame: At baseline, after 26 weeks and after 52 weeks
Results and safety
The study was stopped early (reason given: Terminated because of insufficient number of subjects included.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nicolaas C Schaper, Prof., MD principal investigator
Maastricht University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Liraglutide and NEAT in people with Type 2 Diabetes Mellitus, run by Maastricht University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Terminated because of insufficient number of subjects included.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in HbA1c from baseline and end of treatment (26 weeks) and end of follow-up (52 weeks) (time frame: 6 times, screening, week 0, week 13-26-39-52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2013.