Type 2 DiabetesPhase 4BOLTNCT01755572
Blood Pressure Outcomes With Liraglutide Therapy
A Phase 4 study testing Liraglutide in people with Type 2 Diabetes and Systolic Hypertension, run by Mount Sinai Hospital, Canada at 1 site in Canada.
Trial summary
Purpose: The purpose of this study is to further study the mechanism by which liraglutide, a relatively new anti-hyperglycemic medication, might lower blood pressure in patients with Type 2 diabetes and high blood pressure. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Type 2 Diabetes, Systolic Hypertension
- What is being tested?
- Liraglutide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2013to Mar 2014
- 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 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women between the ages of 30-70.
- Patients with Type 2 Diabetes [diagnosed by their physician] with a serum HbA1c ≥ 6.5% and ≤ 10%.
- Patients currently prescribed 0-2 oral hypoglycemic agents by their physician.
- Patients with systolic blood pressure ≥ 130 mmHg and ≤ 180 mmHg measured by an automated oscillometric blood pressure device [BPTru® or DinaMAP®].
Who cannot join
- Individuals with Type 1 Diabetes, [or secondary forms of diabetes including gestational diabetes, transplant-associated, glucocorticoid-associated, latent-onset diabetes of the adult, or known monogenic forms of diabetes].
- Elevated LVEDP (left ventricular end-diastolic pressure) including congestive heart failure, cardiomyopathy, atrial fibrillation, any valvular heart disease (rated by echocardiography and/or clinically by a cardiologist as moderate or severe in nature), and or elevated RVEDP (right ventricular end-diastolic pressure) including pulmonary hypertension.
- Moderate renal failure or dysfunction as indicated by a serum creatinine >150 μmol/l, and/or an estimated GFR (Glomerular Filtration Rate) less than 59 ml/min per 1.73m2.
- Individuals with secondary forms of hypertension including primary hyperaldosteronism, renal artery stenosis, obstructive sleep apnea, pheochromocytoma, hyperthyroidism, acromegaly, exogenous systemic glucocorticoid use, hypercortisolism.
- Current pregnancy, or recent pregnancy within the last 3 months, or current breast-feeding. Female patients of child bearing potential [premenopausal, or not surgically sterile] who are unwillingly to have a baseline serum pregnancy test, and/or who are unwillingly to use active contraception throughout the duration of the study.
- Use within the last 3 months of any DPP-IV (Dipeptidyl Peptidase) inhibitor, GLP-1 receptor agonist [liraglutide, exenatide (ExBID, or Ex QW)], or insulin [bolus, pre-mixed, or prandial].
Show all 16Show fewer
- Liver failure, including liver cirrhosis or non-alcoholic fatty liver disease.
- Dependence upon alcohol, >14 servings per week if male, >9 servings per week if female.
- Prior history of any clinical presentation consistent with pancreatitis [acute or chronic], or a history of medullary thyroid cancer, c-cell hyperplasia or history of multiple endocrine neoplasia syndromes which predisposes to medullary thyroid cancer [Multiple Endocrine Neoplasia Type 2].
- Individuals with severe systolic hypertension, SBP (systolic blood pressure) ≥ 181 mmHg measured by an automated oscillometric blood pressure device [BPTru® or DinaMAP®].
- Individuals with severe diastolic hypertension, DBP (diastolic blood pressure) ≥ 100 mmHg measured by an automated oscillometric blood pressure device [BPTru® or DinaMAP®].
- Individuals currently prescribed an insulin secretagogue [sulphonylurea] unwillingly to decrease their dose by 50% prior to the start of, and for the duration of the study.
- Individuals with resting tachycardia of >100 bpm or individuals who have a prior history of known conduction abnormalities associated with tachycardia including atrial fibrillation, atrial flutter, prolongation of PR interval, or ventricular tachycardias.
- Current involvement, or any recent involvement [within 3 months] in any other clinical trial involving an investigational product.
- Unwillingness to perform daily sc injection with study drug therapy for duration of 21 days throughout 2 treatment phases.
- Individuals who are currently taking or who have taken diuretic therapy in the past 3 months.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Canada
Toronto, Ontario
About this study
Official title: Hormonal Regulation of Systolic Blood Pressure in Response to the GLP-1 (Glucagon-Like Peptide-1) Receptor Agonist, Liraglutide.
Purpose:
The purpose of this study is to further study the mechanism by which liraglutide, a relatively new anti-hyperglycemic medication, might lower blood pressure in patients with Type 2 diabetes and high blood pressure.
Read the detailed description
Background: Type 2 diabetes is a worldwide health problem. As the reduction in blood pressure has been coupled to improvements in overall cardiovascular outcomes, the control of hypertension has become an important modifiable risk factor in the overall care of the patient with Type 2 Diabetes, in addition to glycemic control. Recently, several large-scale clinical trials evaluating the glucose-lowering effects of the anti-hyperglycemic agent, liraglutide (a glucagon-like peptide-1 receptor agonist), have demonstrated a modest yet persistent anti-hypertensive effect in patients with Type 2 diabetes.
Study Objectives: Accordingly, the goal of this small study is to understand whether the blood pressure lowering effect of liraglutide is coupled to the release of vasoactive mediators which may stimulate natriuresis and/or diuresis and lower systolic blood pressure.
Study Design: Randomized, double-masked, cross-over study with treatment of liraglutide or placebo for 3 weeks, with an intervening washout period for 3 weeks, and cross-over to identical treatment with placebo or liraglutide for 3 weeks.
Study Patients: 20 patients with Type 2 Diabetes and Systolic Hypertension
Endpoints: Change in vasoactive hormones, 24-hour ambulatory blood pressure, urinary sodium excretion patterns.
- Conditions
- Type 2 Diabetes, Systolic Hypertension
- Being tested
- Liraglutide, Placebo
- Keywords
- Type 2 Diabetes, Hypertension, Liraglutide, GLP-1
- Medical subject headings
- Diabetes Mellitus, Type 2, Isolated Systolic Hypertension, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Also called Victoza
Single cross-over study, 1 arm starting with liraglutide for 3 weeks crossed-over to placebo for 3 weeks, and 1 arm starting with placebo with cross-over to liraglutide for 3 weeks.
PlaceboDrug
Single cross-over study, 1 arm starting with liraglutide for 3 weeks crossed-over to placebo for 3 weeks, and 1 arm starting with placebo with cross-over to liraglutide for 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide | Experimental | Liraglutide 0.6mg for 7 days, liraglutide 1.2mg for 7 days, liraglutide 1.8mg for 7 days Receives: Drug: Liraglutide; Drug: Placebo |
| Placebo | Placebo comparator | Placebo 0.6mg sc for 3 weeks, Placebo 1.2mg sc for 3 weeks, Placebo 1.8mg for 3 weeks. Receives: Drug: Liraglutide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma ANP level at 1 Day
+16.72 pg/mL, P = 0.24, 95% CI [-12.1, +45.5] at 2 hours
Measured: Change from Baseline compared in plasma ANP following 1 dose of liraglutide (0.6 mg) compared to crossover treatment with placebo at the 2-hour timepoint
Change in plasma ANP level at 21 Days
-17.42 pg/mL, 95% CI [-36.0, +1.21] at 2 hours
Measured: Change from Baseline in plasma ANP following 21 days of liraglutide (titrated to 1.8 mg) compared to crossover treatment with placebo at the 2-hour timepoint
Secondary outcomes (8)
Change in mean 24-Hr urinary sodium excretion rate following 21 days of liraglutide (titrated 1.8mg) compared to crossover with placebo (baseline-subtracted)
median change +14.18 mmol/L liraglutide vs. placebo (statistically significant, Wilcoxon rank sum)
Measured: 21 days
Change in mean Nighttime urinary sodium excretion rate following 21 days of liraglutide (titrated 1.8mg) compared to crossover with placebo (baseline-subtracted)
median change +4.24 mmol/L nighttime, liraglutide vs. placebo (statistically significant, Wilcoxon Rank Sum)
Measured: 21 days
Change in mean 24-Hr systolic BP, liraglutide compared to crossover with placebo (baseline-subtracted)
+2.33 ± 1.67, p=0.18;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Measured: 21 days
Change in mean 24-hr diastolic BP, liraglutide compared to crossover with placebo (baseline-subtracted)
+3.78 ± 1.34, p=0.01;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Measured: 21 days
Change in mean 24-hr HR, liraglutide compared to crossover with placebo (baseline-subtracted)
+5.21 ± 2.42, p=0.05; Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Measured: 21 days
Office-measured systolic BP; Treatment difference for liraglutide compared to crossover with placebo
-2.35 mmHg (3.49), p=0.51;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Measured: 21 days
Office-measured diastolic BP;Treatment difference for liraglutide compared to crossover with placebo
+3.6 mmHg (2.33), p=0.14;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Measured: 21 days
Office-measured heart rate;Treatment difference for liraglutide compared to crossover with placebo
+9.25 (3.51), p=0.02;Treatment difference liraglutide (1.8 mg) vs. placebo LSMD (±SE), p value
Measured: 21 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2012 (estimated)
- Study startJan 2013
- Primary completionJan 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Collaborators
- Novo Nordisk A/S
- Responsible party
- Sponsor
- Investigators
- Dr. Daniel J. Drucker, MD, Principal investigator, Samuel Lunenfeld Research InstituteDr. Julie A. Lovshin, MD, PhD, Study director, Samuel Lunenfeld Research InstituteDr. Bernard Zinman, MD, Study director, Leadership Sinai Centre for DiabetesDr. Alexander A. Logan, MD, Study director, Samuel Lunenfeld Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01755572
- Sponsor's protocol ID
- MSH-12-0020-A
- Acronym
- BOLT
- Status last verified
- Mar 2015
- First submitted
- 19 Dec 2012
- Last updated
- 25 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Lovshin JA, Barnie A, DeAlmeida A, Logan A, Zinman B, Drucker DJ. Liraglutide promotes natriuresis but does not increase circulating levels of atrial natriuretic peptide in hypertensive subjects with type 2 diabetes. Diabetes Care. 2015 Jan;38(1):132-9. doi: 10.2337/dc14-1958. Epub 2014 Nov 20.
PubMed 25414155
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hormonal Regulation of Systolic Blood Pressure in Response to the GLP-1 (Glucagon-Like Peptide-1) Receptor Agonist, Liraglutide.
- ClinicalTrials.gov ID
- NCT01755572
- Acronym / sponsor ID
- BOLT / MSH-12-0020-A
- Conditions
- Type 2 Diabetes, Systolic Hypertension
- Keywords
- Type 2 Diabetes, Hypertension, Liraglutide, GLP-1
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Collaborators
- Novo Nordisk A/S
- Study start
- Jan 2013
- Primary completion
- Jan 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 24 Dec 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.
Purpose:
The purpose of this study is to further study the mechanism by which liraglutide, a relatively new anti-hyperglycemic medication, might lower blood pressure in patients with Type 2 diabetes and high blood pressure.
Detailed description
Background: Type 2 diabetes is a worldwide health problem. As the reduction in blood pressure has been coupled to improvements in overall cardiovascular outcomes, the control of hypertension has become an important modifiable risk factor in the overall care of the patient with Type 2 Diabetes, in addition to glycemic control. Recently, several large-scale clinical trials evaluating the glucose-lowering effects of the anti-hyperglycemic agent, liraglutide (a glucagon-like peptide-1 receptor agonist), have demonstrated a modest yet persistent anti-hypertensive effect in patients with Type 2 diabetes.
Study Objectives: Accordingly, the goal of this small study is to understand whether the blood pressure lowering effect of liraglutide is coupled to the release of vasoactive mediators which may stimulate natriuresis and/or diuresis and lower systolic blood pressure.
Study Design: Randomized, double-masked, cross-over study with treatment of liraglutide or placebo for 3 weeks, with an intervening washout period for 3 weeks, and cross-over to identical treatment with placebo or liraglutide for 3 weeks.
Study Patients: 20 patients with Type 2 Diabetes and Systolic Hypertension
Endpoints: Change in vasoactive hormones, 24-hour ambulatory blood pressure, urinary sodium excretion patterns.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liraglutide | Experimental | Drug: Liraglutide, Drug: PlaceboLiraglutide 0.6mg for 7 days, liraglutide 1.2mg for 7 days, liraglutide 1.8mg for 7 days |
| Placebo | Placebo comparator | Drug: Liraglutide, Drug: PlaceboPlacebo 0.6mg sc for 3 weeks, Placebo 1.2mg sc for 3 weeks, Placebo 1.8mg for 3 weeks. |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women between the ages of 30-70.
- Patients with Type 2 Diabetes [diagnosed by their physician] with a serum HbA1c ≥ 6.5% and ≤ 10%.
- Patients currently prescribed 0-2 oral hypoglycemic agents by their physician.
- Patients with systolic blood pressure ≥ 130 mmHg and ≤ 180 mmHg measured by an automated oscillometric blood pressure device [BPTru® or DinaMAP®].
Key exclusion criteria (16 listed)
- Individuals with Type 1 Diabetes, [or secondary forms of diabetes including gestational diabetes, transplant-associated, glucocorticoid-associated, latent-onset diabetes of the adult, or known monogenic forms of diabetes].
- Elevated LVEDP (left ventricular end-diastolic pressure) including congestive heart failure, cardiomyopathy, atrial fibrillation, any valvular heart disease (rated by echocardiography and/or clinically by a cardiologist as moderate or severe in nature), and or elevated RVEDP (right ventricular end-diastolic pressure) including pulmonary hypertension.
- Moderate renal failure or dysfunction as indicated by a serum creatinine >150 μmol/l, and/or an estimated GFR (Glomerular Filtration Rate) less than 59 ml/min per 1.73m2.
- Individuals with secondary forms of hypertension including primary hyperaldosteronism, renal artery stenosis, obstructive sleep apnea, pheochromocytoma, hyperthyroidism, acromegaly, exogenous systemic glucocorticoid use, hypercortisolism.
- Current pregnancy, or recent pregnancy within the last 3 months, or current breast-feeding. Female patients of child bearing potential [premenopausal, or not surgically sterile] who are unwillingly to have a baseline serum pregnancy test, and/or who are unwillingly to use active contraception throughout the duration of the study.
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: VictozaSingle cross-over study, 1 arm starting with liraglutide for 3 weeks crossed-over to placebo for 3 weeks, and 1 arm starting with placebo with cross-over to liraglutide for 3 weeks. | Drug | Liraglutide, Placebo |
| PlaceboSingle cross-over study, 1 arm starting with liraglutide for 3 weeks crossed-over to placebo for 3 weeks, and 1 arm starting with placebo with cross-over to liraglutide for 3 weeks. | Drug | Liraglutide, Placebo |
Primary outcome
Change in plasma ANP level at 1 Day
Time frame: Change from Baseline compared in plasma ANP following 1 dose of liraglutide (0.6 mg) compared to crossover treatment with placebo at the 2-hour timepoint
+16.72 pg/mL, P = 0.24, 95% CI [-12.1, +45.5] at 2 hours
Change in plasma ANP level at 21 Days
Time frame: Change from Baseline in plasma ANP following 21 days of liraglutide (titrated to 1.8 mg) compared to crossover treatment with placebo at the 2-hour timepoint
-17.42 pg/mL, 95% CI [-36.0, +1.21] at 2 hours
8 secondary outcomes
Change in mean 24-Hr urinary sodium excretion rate following 21 days of liraglutide (titrated 1.8mg) compared to crossover with placebo (baseline-subtracted)
Time frame: 21 days
Change in mean Nighttime urinary sodium excretion rate following 21 days of liraglutide (titrated 1.8mg) compared to crossover with placebo (baseline-subtracted)
Time frame: 21 days
Change in mean 24-Hr systolic BP, liraglutide compared to crossover with placebo (baseline-subtracted)
Time frame: 21 days
Change in mean 24-hr diastolic BP, liraglutide compared to crossover with placebo (baseline-subtracted)
Time frame: 21 days
Change in mean 24-hr HR, liraglutide compared to crossover with placebo (baseline-subtracted)
Time frame: 21 days
Office-measured systolic BP; Treatment difference for liraglutide compared to crossover with placebo
Time frame: 21 days
Office-measured diastolic BP;Treatment difference for liraglutide compared to crossover with placebo
Time frame: 21 days
Office-measured heart rate;Treatment difference for liraglutide compared to crossover with placebo
Time frame: 21 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2015.
- Results publication: PubMed 25414155Lovshin JA, Barnie A, DeAlmeida A, Logan A, Zinman B, Drucker DJ. Liraglutide promotes natriuresis but does not increase circulating levels of atrial natriuretic peptide in hypertensive subjects with type 2 diabetes. Diabetes Care. 2015 Jan;38(1):132-9. doi: 10.2337/dc14-1958. Epub 2014 Nov 20.
Related trials for Type 2 Diabetes
Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)
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
Not yet recruiting
Impact of Endoscopic Sleeve Gastroplasty (ESG) in Obese Adults With Type 2 Diabetes (T2D)
Type 2 Diabetes Mellitus (T2D), Obesity (BMI>30)
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.
Dr. Daniel J. Drucker, MD principal investigator
Samuel Lunenfeld Research Institute
Dr. Julie A. Lovshin, MD, PhD study director
Samuel Lunenfeld Research Institute
Dr. Bernard Zinman, MD study director
Leadership Sinai Centre for Diabetes
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 and Systolic Hypertension, run by Mount Sinai Hospital, Canada at 1 site in Canada.
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 16 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 25 Mar 2015. 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 Canada. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 plasma ANP level at 1 Day (time frame: Change from Baseline compared in plasma ANP following 1 dose of liraglutide (0.6 mg) compared to crossover treatment with placebo at the 2-hour timepoint). 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?
On the ClinicalTrials.gov record for NCT01755572, which also lists 1 linked publication.
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 25 Mar 2015.