Type 1 Diabetes1974NCT02777073
Effects of Single Doses of Liraglutide and Dapagliflozin on Ketogenesis in Type 1 Diabetes
A study testing Victoza and Dapagliflozin 10mg Tab in people with Type 1 Diabetes, run by University at Buffalo at 1 site in United States.
Trial summary
1. To compare levels of ketone bodies (beta-hydroxybutyrate and acetoacetate) in plasma and urine following a single dose treatment of either liraglutide 1.8mg, dapagliflozin 10mg or placebo in insulinopenic state. 2. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Victoza and Dapagliflozin 10mg Tab
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2016to 31 Dec 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 Diabetes on continuous subcutaneous insulin infusion (CSII, also known as insulin pump).
- Undetectable c peptide (c-peptide < 0.1 ng/ml).
- HbA1c of less than or equal to 8.5%.
- Age 18-75 inclusive
Who cannot join
- Type 1 diabetes for less than 12 months
- Coronary event/ procedure (MI, Unstable angina, CABG, PCI) in the last four weeks
- Hepatic disease (Transaminase > 3 times normal) or Cirrhosis
- Renal impairment (serum eGFR <30ml/min/1.73m2)
- HIV or Hepatitis B or C positive status
- History of pancreatitis, i.e., history of gallstones, alcohol abuse and hypertriglyceridemia
Show all 13Show fewer
- Pregnancy
- Inability to give informed consent
- History of Gastroparesis
- Personal or Family History of medullary thyroid carcinoma or MEN 2 syndrome
- Alcoholism
- Hypertriglyceridemia (>500 mg/dl).
- Those with history of bladder cancer , diabetic ketoacidosis
Trial locations and contacts
1 site in 1 country.
United States1 site
ECMC Ambulatory Center, 3rd Floor
Buffalo, New York, 14215
About this study
Official title: Effects of Single Doses of Liraglutide and Dapagliflozin on Hyperglycemia and Ketogenesis in Type 1 Diabetes
- To compare levels of ketone bodies (beta-hydroxybutyrate and acetoacetate) in plasma and urine following a single dose treatment of either liraglutide 1.8mg, dapagliflozin 10mg or placebo in insulinopenic state.
- To compare plasma levels of free fatty acid, glucagon, hs-CRP, Ll-6 and IL-1 before and after administration of liraglutide/placebo.
Read the detailed description
Diabetic ketoacidosis is an important cause of mortality and morbidity in type 1 patients. The decreased ratio of insulin to glucagon in insulin deficient subjects promotes ketogenesis. In patients with type 1 diabetes, the suppressive effect of hyperglycemia and the paracrine inhibitory effect of insulin and GABA from the β cell on α cell are absent. Thus, plasma glucagon concentrations are elevated and in combination with insulin deficiency, lead to lipolysis, increased plasma FFA concentrations and an increased fatty acid supply to the liver. Thus, both fatty acid oxidation and ketogenesis are enhanced.
Our recent work has shown that liraglutide, a GLP 1 agonist, improves glycemic control and reduces glycemic excursions in patients with type 1 diabetes within a few days of the initiation of treatment.
With this background, the investigators hypothesize that suppression of glucagon with liraglutide in patients with type 1 diabetes may protect them from lipolysis, increased bio-availability of FFAs, ketogenesis and ketoacidosis.
It is essential to investigate this area further as there are no prior studies that have investigated the acute effects of liraglutide on FFAs or ketogenesis. This study will be the first randomized controlled prospective study investigating the effect of liraglutide on ketogenesis. Also, it would be important to measure the mediators of inflammation at the same time to investigate whether there is a concomitant changes of inflammatory factors in parallel with the lipolysis and ketogenesis.
After the screening visit, subjects who meet the inclusion and exclusion criteria will be randomized to receive a single dose of either liraglutide, dapagliflozin or placebo and will be monitored for a total of 8 hours.
- Conditions
- Type 1 Diabetes
- Being tested
- Victoza, Placebo, Dapagliflozin 10mg Tab
- Keywords
- Diabetic ketoacidosis, Insulin, Type 1 Diabetes, glucose (sugar) control
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetic Ketoacidosis, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VictozaDrug
Also called Liraglutide
Single dose of Liraglutide
PlaceboDrug
Single dose of generic placebo
Dapagliflozin 10mg TabDrug
Also called Dapagliflozin
single dose of 10 mg dapagliflozin
| Study group | Role | What they receive |
|---|---|---|
| liraglutide 1.8 mg | Active comparator | single dose of Victoza ( liraglutide) 1.8 mg Receives: Drug: Victoza |
| Placebo | Placebo comparator | Single dose of placebo Receives: Drug: Placebo |
| Dapagliflozin | Active comparator | Single dose of Dapagliflozin 10 mg oral tablet Receives: Drug: Dapagliflozin 10mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Ketone Bodies Formation After Single Dose of Liraglutide and Dapagliflozin
To compare levels of ketone bodies beta-hydroxybutyrate in plasma following a single dose treatment of either liraglutide 1.8mg,dapagliflozin 10mg or placebo in insulinopenic state.
Measured: 8 hours
Secondary outcomes (3)
Change in Glucagon Levels.
This secondary endpoint compares change in glucagon concentrations (in pg/ml) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo
Measured: 8 hours
Change in Free Fatty Acid (FFA) Concentrations
This secondary endpoint compares the change in FFA concentrations (mM) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo
Measured: 8 hours
Change in Ghrelin Concentrations
This secondary endpoint compares the change in ghrelin concentrations (pg/ml) from baseline at 8 hours following liraglutide and dapagliflozin compared to placebo
Measured: 8 Hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2016 (estimated)
- Study start1 Mar 2016
- Primary completion1 Dec 2016
- Study completion31 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University at Buffalo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paresh Dandona, University at Buffalo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02777073
- Sponsor's protocol ID
- 1974
- Acronym
- 1974
- Status last verified
- Feb 2024
- First submitted
- 1 Dec 2015
- Last updated
- 29 Feb 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Single Doses of Liraglutide and Dapagliflozin on Hyperglycemia and Ketogenesis in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT02777073
- Acronym / sponsor ID
- 1974 / 1974
- Conditions
- Type 1 Diabetes
- Keywords
- Diabetic ketoacidosis, Insulin, Type 1 Diabetes, glucose (sugar) control
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University at BuffaloUniversity, hospital or other
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- 1 Dec 2016 (actual)
- Study completion
- 31 Dec 2016 (actual)
- First posted
- 19 May 2016 (estimated)
- Results
- Posted 29 Feb 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- To compare levels of ketone bodies (beta-hydroxybutyrate and acetoacetate) in plasma and urine following a single dose treatment of either liraglutide 1.8mg, dapagliflozin 10mg or placebo in insulinopenic state.
- To compare plasma levels of free fatty acid, glucagon, hs-CRP, Ll-6 and IL-1 before and after administration of liraglutide/placebo.
Detailed description
Diabetic ketoacidosis is an important cause of mortality and morbidity in type 1 patients. The decreased ratio of insulin to glucagon in insulin deficient subjects promotes ketogenesis. In patients with type 1 diabetes, the suppressive effect of hyperglycemia and the paracrine inhibitory effect of insulin and GABA from the β cell on α cell are absent. Thus, plasma glucagon concentrations are elevated and in combination with insulin deficiency, lead to lipolysis, increased plasma FFA concentrations and an increased fatty acid supply to the liver. Thus, both fatty acid oxidation and ketogenesis are enhanced.
Our recent work has shown that liraglutide, a GLP 1 agonist, improves glycemic control and reduces glycemic excursions in patients with type 1 diabetes within a few days of the initiation of treatment.
With this background, the investigators hypothesize that suppression of glucagon with liraglutide in patients with type 1 diabetes may protect them from lipolysis, increased bio-availability of FFAs, ketogenesis and ketoacidosis.
It is essential to investigate this area further as there are no prior studies that have investigated the acute effects of liraglutide on FFAs or ketogenesis. This study will be the first randomized controlled prospective study investigating the effect of liraglutide on ketogenesis. Also, it would be important to measure the mediators of inflammation at the same time to investigate whether there is a concomitant changes of inflammatory factors in parallel with the lipolysis and ketogenesis.
After the screening visit, subjects who meet the inclusion and exclusion criteria will be randomized to receive a single dose of either liraglutide, dapagliflozin or placebo and will be monitored for a total of 8 hours.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| liraglutide 1.8 mg | Active comparator | Drug: Victozasingle dose of Victoza ( liraglutide) 1.8 mg |
| Placebo | Placebo comparator | Drug: PlaceboSingle dose of placebo |
| Dapagliflozin | Active comparator | Drug: Dapagliflozin 10mg TabSingle dose of Dapagliflozin 10 mg oral tablet |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Type 1 Diabetes on continuous subcutaneous insulin infusion (CSII, also known as insulin pump).
- Undetectable c peptide (c-peptide < 0.1 ng/ml).
- HbA1c of less than or equal to 8.5%.
- Age 18-75 inclusive
Key exclusion criteria (13 listed)
- Type 1 diabetes for less than 12 months
- Coronary event/ procedure (MI, Unstable angina, CABG, PCI) in the last four weeks
- Hepatic disease (Transaminase > 3 times normal) or Cirrhosis
- Renal impairment (serum eGFR <30ml/min/1.73m2)
- HIV or Hepatitis B or C positive status
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 |
|---|---|---|
| VictozaAlso: LiraglutideSingle dose of Liraglutide | Drug | liraglutide 1.8 mg |
| PlaceboSingle dose of generic placebo | Drug | Placebo |
| Dapagliflozin 10mg TabAlso: Dapagliflozinsingle dose of 10 mg dapagliflozin | Drug | Dapagliflozin |
Primary outcome
Difference in Ketone Bodies Formation After Single Dose of Liraglutide and Dapagliflozin
Time frame: 8 hours
To compare levels of ketone bodies beta-hydroxybutyrate in plasma following a single dose treatment of either liraglutide 1.8mg,dapagliflozin 10mg or placebo in insulinopenic state.
3 secondary outcomes
Change in Glucagon Levels.
Time frame: 8 hours
Change in Free Fatty Acid (FFA) Concentrations
Time frame: 8 hours
Change in Ghrelin Concentrations
Time frame: 8 Hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Feb 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Type 1 Diabetes
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 1
Pharmacokinetics, Safety, and Immunogenicity Comparison of Bmab1700 and Opdivo® as Adjuvant Monotherapy in Participants With Melanoma
Melanoma
Active, not recruitingPhase 2
A Study of Botensilimab and Balstilimab for the Treatment of Colorectal Cancer
Metastatic Colorectal Cancer
Not yet recruiting
Inter-Arm Differences in Continuous Glucose Monitor Readings in Adults With Diabetes
Continuous Glucose Monitoring, Type 1 Diabetes
RecruitingObservational study
Estimated Risk of Preeclampsia in the First Trimester and Its Association With Subclinical Atherosclerosis and Cardiovascular Risk in Women With Type 1 Diabetes
Type 1 Diabetes, Preeclampsia
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Victoza and Dapagliflozin 10mg Tab in people with Type 1 Diabetes, run by University at Buffalo 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 4 inclusion and 13 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: finished, as of the sponsor's last update on 29 Feb 2024. 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. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Difference in Ketone Bodies Formation After Single Dose of Liraglutide and Dapagliflozin (time frame: 8 hours). 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 29 Feb 2024.