Type 2 DiabetesPhase 4NCT02198209
Liraglutide Actions on the Liver: Effects on Glucose Phosphorylation
A Phase 4 study testing Liraglutide in people with Type 2 Diabetes, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial summary
Type 2 diabetes is a chronic disease that has reached epidemic proportions. In order to improve our strategies for preventing and treating type 2 diabetes the investigators need to better understand the mechanism of this disease, and the way in which current therapies, such as the drug liraglutide, work to control… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Liraglutide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2019to Dec 2020
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18- 65 years of age (inclusive)
- Ability to provide informed consent before any trial-related activities
- Ability to communicate effectively with research staff
- Ability to return for follow up visit
- Adequate IV access
- If a female of childbearing potential, non-pregnant and taking reliable contraception
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- Documented T2DM (per most recent American Diabetes Association criteria);
- Drug naïve or treated with metformin only;
- Diabetes should be well controlled (as defined by HbA1 ≤ 7.5%, FPG <180 mg/dl).
Who cannot join
- Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures
- Presence of cancer or any clinically significant cardiac, respiratory, renal, hepatic, gastrointestinal, endocrinological, haematological, neurological, or psychiatric diseases or disorders (inclusion will be discussed with attending physician)
- Liver disease; history of alcoholism.
- Known or suspected allergy to liraglutide
- Contraindications to liraglutide: patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2
- Patients with a history of pancreatitits
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- Patients that have been treated with drugs that promote weight loss (e.g., Xenical® [orlistat], Meridia® [sibutramine], Acomplia® [rimonabant], Acutrim® [phenylpropanolamine], or similar over-the-counter medications) within 3 months of study start
- Patients that have been treated with diabetes drugs: injectables, (e.g GLP-1R agonists (Byetta® [exenatide], Victoza® [liraglutide]) amylin analogues; insulin and insulin analogues) or oral agents other than metformin (e.g.DPP-IV- inhibitors (Januvia® [sitagliptin], Onglyza® [saxagliptin] or Janumet® [sitagliptin and metformin]),insulin sensitizers (thiazolidindiones: pioglitazone [Actos®]); or sulfonylureas) within 3 months of study start.
- The receipt of any investigational drug within 3 months prior to study start.
- Type 1 diabetes
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars Sinai Medical Center
Los Angeles, California, 90048
About this study
Type 2 diabetes is a chronic disease that has reached epidemic proportions. In order to improve our strategies for preventing and treating type 2 diabetes the investigators need to better understand the mechanism of this disease, and the way in which current therapies, such as the drug liraglutide, work to control blood sugar. It is known that liraglutide acts via increasing the secretion of the hormone insulin from the pancreas, hormone that in turn controls blood sugar. However, it is not known whether liraglutide also has actions on the liver. Animal studies have suggested that liraglutide might act by controlling the liver enzyme glucokinase (GCK), an enzyme that increases blood sugar uptake by the liver. This could be a crucial mechanism in which liraglutide controls blood sugar independently of insulin, thus making it beneficial not only in type 2 but also in type 1 diabetes. The effect of liraglutide on GCK activity has not been yet measured in humans. The investigators propose to investigate the acute and chronic effect of liraglutide on GCK by using a simple, widely used procedure (an IntraVenous Glucose Tolerance Test-IVGTT) and a novel approach (mathematical modeling of data obtained from this procedure), to assess GCK activity in people with type 2 diabetes. The investigators will first compare data obtained form 2 IVGTTs (with and without liraglutide) performed 1 week apart (acute effect). The investigators will then give liraglutide to patients for 6 weeks and do another IVGTT to measure GCK activity (chronic effects). Data obtained from this study will be used to further understand the mechanism of liraglutide action and how to better employ our current therapeutic options and develop new strategies for preventing and treating diabetes.
Read the detailed description
It is known that liraglutide impacts favorably glucose homeostasis in type 2 diabetic patients, but not the exact mechanism of this effect. In particular, liraglutide's acute and chronic effects on the liver are not well understood. The aim of our study is to determine whether liraglutide acutely and/or chronically changes hepatic GCK activity in vivo in type 2 diabetic patients, and to quantify this effect. We hypothesize that liraglutide increases GCK activity and that this results in increased hepatic glucose uptake, contributing to a lowering of glycemia.
Our specific aims are:
- to measure liraglutide's acute effect on GCK activity changes in vivo in type 2 diabetic patients;
- to assess whether chronic treatment with liraglutide determines a change in liver GCK activity in type 2 diabetic patients, as assessed during an IVGTT.
We expect that liraglutide acutely and/or chronically increases GCK activity, thus contributing to higher liver glucose uptake and lower glycemia.
Primary endpoints
- GCK activity (acute effect) during IVGTTs with and without liraglutide administration. GCK activity will be calculated based on lactate and glucose measurements during the IVGTT
- GCK activity during IVGTTs before and after 6 weeks of liraglutide treatment (IVGTT3).
Secondary endpoints
- SI-IVGTT (insulin sensitivity during an intravenous glucose tolerance test) as quantified by the MINMOD analysis of the IVGTT
- Acute insulin response to glucose (AIRg) and the disposition index (DI-MINMOD), the ability of beta cell to compensate for changes in insulin sensitivity.
This is a study designed to investigate the effect of liraglutide in type 2 diabetes therefore subjects are selected from type 2 diabetes population of the Los Angeles basin area. The study population is represented by type 2 diabetics (age 18-65 y old, T2DM diagnosed by current American Diabetes Association diagnostic criteria ( HbA1c ≥ 6.5 % or fasting plasma glucose ≥ 126 mg/dl or 2h plasma glucose ≥ 200 mg/dL during an OGTT or in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis a random plasma glucose ≥ 200 mg/dl).
- Conditions
- Type 2 Diabetes
- Being tested
- Liraglutide
- Keywords
- liraglutide, GLP-1, liver glucokinase
- Medical subject headings
- Diabetes Mellitus, Type 2, Maturity-Onset Diabetes of the Young, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Also called Victoza
- acute study: one injection of 0.6 mg s.c. before IVGTT
- chronic study: 6 weeks of daily liraglutide administration (1 week at 0.6 mg, 1 week at 1.2 mg, 4 weeks at 1.8 mg, s.c).
| Study group | Role | What they receive |
|---|---|---|
| single arm | Other | Liraglutide (Victoza)
1. acute study: one injection of 0.6 mg s.c. before IVGTT
2. chronic study: 6 weeks of daily liraglutide administration (1 week at 0.6 mg, 1 week at 1.2 mg, 4 weeks at 1.8 mg, s.c). Receives: Drug: Liraglutide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver glucokinase activity (acute effect)
We will measure liver glucokinase (GCK) activity 'in vivo' during IVGTTs with and without liraglutide administration
Measured: 12 months
Liver glucokinase activity (chronic effect)
We will measure liver glucokinase (GCK) activity 'in vivo' during IVGTTs before and after 6 weeks of daily liraglutide administration
Measured: 12 months
Secondary outcomes (2)
insulin sensitivity
We will measure SI-IVGTT (insulin sensitivity during an intravenous glucose tolerance test) as quantified by the MINMOD analysis of the IVGTT.
Measured: 12 months
Acute insulin response to glucose and the disposition index
We will assess the acute insulin response to glucose (AIRg) and the disposition index (DI-MINMOD)(the ability of beta cell to compensate for changes in insulin sensitivity)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2014 (estimated)
- Study startDec 2019 (estimated)
- Primary completionJul 2020 (estimated)
- Study completionDec 2020 (estimated)
Why it stopped: Investigator decided not to move forward with study prior to study start date
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marilyn Ader, PhD, Cedars-Sinai Medical Center
- Investigators
- Viorica Ionut, MD PhD, Principal investigator, Cedars-Sinai Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02198209
- Sponsor's protocol ID
- U1111-1138-7223
- Status last verified
- Sep 2019
- First submitted
- 21 Jul 2014
- Last updated
- 30 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liraglutide Actions on the Liver: Effects on Glucose Phosphorylation
- ClinicalTrials.gov ID
- NCT02198209
- Acronym / sponsor ID
- U1111-1138-7223
- Conditions
- Type 2 Diabetes
- Keywords
- liraglutide, GLP-1, liver glucokinase
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Investigator decided not to move forward with study prior to study start date
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Study start
- Dec 2019 (estimated)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 23 Jul 2014 (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.
Type 2 diabetes is a chronic disease that has reached epidemic proportions. In order to improve our strategies for preventing and treating type 2 diabetes the investigators need to better understand the mechanism of this disease, and the way in which current therapies, such as the drug liraglutide, work to control blood sugar. It is known that liraglutide acts via increasing the secretion of the hormone insulin from the pancreas, hormone that in turn controls blood sugar. However, it is not known whether liraglutide also has actions on the liver. Animal studies have suggested that liraglutide might act by controlling the liver enzyme glucokinase (GCK), an enzyme that increases blood sugar uptake by the liver. This could be a crucial mechanism in which liraglutide controls blood sugar independently of insulin, thus making it beneficial not only in type 2 but also in type 1 diabetes. The effect of liraglutide on GCK activity has not been yet measured in humans. The investigators propose to investigate the acute and chronic effect of liraglutide on GCK by using a simple, widely used procedure (an IntraVenous Glucose Tolerance Test-IVGTT) and a novel approach (mathematical modeling of data obtained from this procedure), to assess GCK activity in people with type 2 diabetes. The investigators will first compare data obtained form 2 IVGTTs (with and without liraglutide) performed 1 week apart (acute effect). The investigators will then give liraglutide to patients for 6 weeks and do another IVGTT to measure GCK activity (chronic effects). Data obtained from this study will be used to further understand the mechanism of liraglutide action and how to better employ our current therapeutic options and develop new strategies for preventing and treating diabetes.
Detailed description
It is known that liraglutide impacts favorably glucose homeostasis in type 2 diabetic patients, but not the exact mechanism of this effect. In particular, liraglutide's acute and chronic effects on the liver are not well understood. The aim of our study is to determine whether liraglutide acutely and/or chronically changes hepatic GCK activity in vivo in type 2 diabetic patients, and to quantify this effect. We hypothesize that liraglutide increases GCK activity and that this results in increased hepatic glucose uptake, contributing to a lowering of glycemia.
Our specific aims are:
- to measure liraglutide's acute effect on GCK activity changes in vivo in type 2 diabetic patients;
- to assess whether chronic treatment with liraglutide determines a change in liver GCK activity in type 2 diabetic patients, as assessed during an IVGTT.
We expect that liraglutide acutely and/or chronically increases GCK activity, thus contributing to higher liver glucose uptake and lower glycemia.
Primary endpoints
- GCK activity (acute effect) during IVGTTs with and without liraglutide administration. GCK activity will be calculated based on lactate and glucose measurements during the IVGTT
- GCK activity during IVGTTs before and after 6 weeks of liraglutide treatment (IVGTT3).
Secondary endpoints
- SI-IVGTT (insulin sensitivity during an intravenous glucose tolerance test) as quantified by the MINMOD analysis of the IVGTT
- Acute insulin response to glucose (AIRg) and the disposition index (DI-MINMOD), the ability of beta cell to compensate for changes in insulin sensitivity.
This is a study designed to investigate the effect of liraglutide in type 2 diabetes therefore subjects are selected from type 2 diabetes population of the Los Angeles basin area. The study population is represented by type 2 diabetics (age 18-65 y old, T2DM diagnosed by current American Diabetes Association diagnostic criteria ( HbA1c ≥ 6.5 % or fasting plasma glucose ≥ 126 mg/dl or 2h plasma glucose ≥ 200 mg/dL during an OGTT or in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis a random plasma glucose ≥ 200 mg/dl).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| single arm | Other | Drug: LiraglutideLiraglutide (Victoza) 1. acute study: one injection of 0.6 mg s.c. before IVGTT 2. chronic study: 6 weeks of daily liraglutide administration (1 week at 0.6 mg, 1 week at 1.2 mg, 4 weeks at 1.8 mg, s.c). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 18- 65 years of age (inclusive)
- Ability to provide informed consent before any trial-related activities
- Ability to communicate effectively with research staff
- Ability to return for follow up visit
- Adequate IV access
Key exclusion criteria (10 listed)
- Pregnant, breast-feeding or the intention of becoming pregnant or not using adequate contraceptive measures
- Presence of cancer or any clinically significant cardiac, respiratory, renal, hepatic, gastrointestinal, endocrinological, haematological, neurological, or psychiatric diseases or disorders (inclusion will be discussed with attending physician)
- Liver disease; history of alcoholism.
- Known or suspected allergy to liraglutide
- Contraindications to liraglutide: patients with a personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2
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 |
|---|---|---|
| LiraglutideAlso: Victoza1. acute study: one injection of 0.6 mg s.c. before IVGTT 2. chronic study: 6 weeks of daily liraglutide administration (1 week at 0.6 mg, 1 week at 1.2 mg, 4 weeks at 1.8 mg, s.c). | Drug | single arm |
Primary outcome
Liver glucokinase activity (acute effect)
Time frame: 12 months
We will measure liver glucokinase (GCK) activity 'in vivo' during IVGTTs with and without liraglutide administration
Liver glucokinase activity (chronic effect)
Time frame: 12 months
We will measure liver glucokinase (GCK) activity 'in vivo' during IVGTTs before and after 6 weeks of daily liraglutide administration
2 secondary outcomes
insulin sensitivity
Time frame: 12 months
Acute insulin response to glucose and the disposition index
Time frame: 12 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2019.
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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.
Viorica Ionut, MD PhD principal investigator
Cedars-Sinai 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 in people with Type 2 Diabetes, run by Cedars-Sinai Medical Center at 1 site in United States.
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 9 inclusion and 10 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: withdrawn, as of the sponsor's last update on 30 Sep 2019. 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 United States. 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. 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 withdrawn before enrolling participants, so there are no results.
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?
Liver glucokinase activity (acute effect) (time frame: 12 months). 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 30 Sep 2019.