Type II Diabetes MellitusPhase 4NCT01969084
The Effect of Linagliptin on Mitochondrial and Endothelial Function
A Phase 4 study testing Linagliptin, Microcirculation testing and Macrocirculation testing in people with Type II Diabetes Mellitus, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
Investigators propose to examine the effect of 12 weeks of Linagliptin, a diabetes drug, treatment on inflammation as well as vascular and mitochondrial function in diabetic patients. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Type II Diabetes Mellitus
- What is being tested?
- Linagliptin, Microcirculation testing and Macrocirculation testing
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to Jul 2016
- Phase
- Phase 4
- 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 30 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with T2DM whose medical or lifestyle treatment regimen is stable and not expected to be changed during the study period. Patients will be considered stable on their treatment regimen if there have not been any changes in the type of their antidiabetic medications over the past 3 months and/or there have not been any changes in their blood glucose levels that have caused them to see their health care provider more often than usual over the preceding three months. The diagnosis of T2DM will be according to the American Diabetes Association criteria. Subjects previously diagnosed with T2DM will not require confirmatory testing.
- Age 30-70 years
- Patients on insulin should be on a stable insulin regimen for at least 4 months prior to enrollment.
- Patients on antidiabetic treatment will be eligible if they are stable and no change in their treatment is planned for the next three months while they are in the study.
- HBA1c ≤ 10.0
Who cannot join
- Patient with unstable diabetes that has resulted in hyperosmolar coma, DKA, and/or documented increase or decrease in HbA1c of more than 2.0% within the previous 6 months
- Treatment with DPP4 Inhibitors or GLP-1 agonists. Patients who discontinued such treatment should be at least free for a 3-month period.
- Severe proliferative retinopathy that renders the subject legally blinded
- Previously intermittent claudication or diagnosed severe peripheral arterial disease requiring intervention.
- History of Deep Vein Thrombosis (DVT) within the past 3 months.
- Significant limb swelling due to lymphedema
Show all 35Show fewer
- Previous diagnosis of severe gastroparesis diabeticorum due to autonomic neuropathy that has necessitated hospital admission
- Presence of non-healing foot ulceration due to severe peripheral diabetic neuropathy
- History of pancreatitis
- Documented diabetic nephropathy manifested as macro-albuminuria before enrollment in the study, (2 of 3 urine specimens collected within a 3-6 month period with urine albumin> 300 ug/mg creatinine - according to the ADA position statement)
- Smokers. Smokers will be defined as any subject who reports tobacco use during the three months before to study enrollment.
- Active or uncontrolled cardiovascular disease as follows:
- Myocardial infarction, or angina within 12 months of study participation
- Arrhythmia (uncontrolled, highly symptomatic, requires treatment or life-threatening).
- Patients with congestive heart failure requiring pharmacologic management, particularly when accompanied by hypoperfusion and hypoxemia due to unstable or acute failure, are at increased risk of lactic acidosis.
- Stroke or transient ischemic attack within 12 months of study participation
- Uncontrolled hypertension: SBP> 180 mmHg or DBP> 105 mmHg (2 abnormal readings during visit)
- Liver disease (AST, ALT Alk Phos levels >2x upper normal limit) at the time of enrollment
- Renal disease (creatinine > 2 mg/dL and/or estimated GFR <30 mL/min, history of dialysis, nephrotic syndrome) at the time of enrollment.
- Severe dyslipidemia (triglycerides>600 mg/dL or cholesterol >350 mg/dL) Subjects with hypertriglyceridemia may be retested in 2-3 weeks as the values can fluctuate tremendously within a few days. In the event that the retested value allows the patient to be enrolled, a planned deviation will be submitted to the CCI.
- Any other serious chronic disease requiring active treatment.
- Pregnancy or Lactation
- Females of childbearing potential not using an effective form of birth control as determined by the investigators.
- Subjects on any of the following medications:
- Systemic (not inhaled) Glucocorticoids
- Antineoplastic agents
- Rifampin
- Patient is known to have a history of immunodeficiency diseases, including a positive HIV (ELISA and Western blot) and/or positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result in the past.
- History of drug or alcohol abuse within the 12 months prior to dosing or evidence of such abuse as indicated by the laboratory assays conducted during the screening or baseline evaluations.
- Acute or chronic metabolic acidosis, including diabetic ketoacidosis.
- History of hypersensitivity reaction to linagliptin (such as urticaria, angioedema, or bronchial hyperreactivity) or metformin.
- Contraindications to MRI: Medically unstable or hematologic, renal, or hepatic dysfunction, cardiac pacemaker, Intracranial clips, metal implants, or external clips within 10 mm of the head,
- Metal in eyes.
- Pregnant or nursing women -
- Claustrophobia.
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
Investigators propose to examine the effect of 12 weeks of Linagliptin, a diabetes drug, treatment on inflammation as well as vascular and mitochondrial function in diabetic patients. Investigators hypothesize that Linagliptin will reduce the proinflammatory state, improve endothelial function, increase the blood flow at the muscle microcirculation level and improve mitochondrial function. In this study, investigators will perform tests that evaluate the function of small and large blood vessels by employing ultrasound and laser doppler techniques. In addition MRI scans that evaluate the mitochondrial function of the lower extremity muscles at rest and during exercise will also be employed. Forty subjects with Type 2 diabetes will be studied for twelve weeks and half of them will be randomly assigned to receive linagliptin while the other half will receive placebo. All tests will be performed at the beginning and the end of the study.
- Conditions
- Type II Diabetes Mellitus
- Being tested
- Linagliptin, Placebo, Microcirculation testing, Macrocirculation testing, MRI Scans
- Keywords
- Type II Diabetes Mellitus, Diabetes, Metabolism, Linagliptin, Tradjenta, Glucose
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LinagliptinDrug
Also called Tradjenta
PlaceboDrug
Microcirculation testingOther
The endothelial function of the micro-circulation will be assessed by measuring the hyperemic response of the vessels in the superficial skin of the forearm after the iontophoresis of acetylcholine. The endothelium independent vasodilation will be assessed by the iontophoresis of sodium nitroprusside. Laser Doppler perfusion imaging will be used to measure relative changes in flow velocity.Visible and NIR Medical Hyperspectral Imaging (MHSI) data will be collected with a HyperMed OxyView MHSI System (HyperMed, Inc., Watertown, MA). MHSI images will be obtained from same forearm area where the iontophoresis of acetylcholine and sodium nitroprusside will be performed, before and after the iontophoresis test.
Macrocirculation testingOther
Use ultrasound to measure brachial artery flow mediated vasodilation (FMD, endothelium-dependent vasodilation) and nitroglycerin induced dilation (NID, endothelium-independent vasodilation).
MRI ScansOther
Phosphorus-31 MRI data will be obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia.
| Study group | Role | What they receive |
|---|---|---|
| Linagliptin | Experimental | Subjects given Linagliptin Receives: Drug: Linagliptin; Other: Microcirculation testing; Other: Macrocirculation testing; Other: MRI Scans |
| Sugar pill | Placebo comparator | Subjects given sugar pill/placebo Receives: Drug: Placebo; Other: Microcirculation testing; Other: Macrocirculation testing; Other: MRI Scans |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phosphocreatine (PCR) Recovery Time After Exhaustive or up to 6 Minutes of Leg Exercise.
Change in the time to phosphocreatine recovery between the baseline visit and post-treatment visit following the graded exercise test.
Measured: Baseline and 12 weeks
Secondary outcomes (4)
Change in Muscle Oxygenation Recovery Time
Change in muscle oxygenation after ischemia inducing occlusion for 4 minutes.
Measured: Baseline and 12 weeks
Changes in Vascular Reactivity in the Micro- and Macro-circulation.
Change in markers of macro- and microvascular function from the baseline visit to the post-treatment visit between the two groups.
Measured: Baseline and 12 weeks
Changes in SDF1-α and Substance P
Measured: Baseline and 12 weeks
Changes in Circulating Endothelial Progenitor Cell Phenotypes
The measurements of the various EPC phenotypes were performed at the Beth Israel Deaconess Flow Cytometry Core Facility. Immunofluorescent cell staining was performed on peripheral blood with the use of the fluorescent conjugated antibodies. 1.000.000 events per sample were acquired using a FACS LSR II analyzer (Becton Dickinson, Franklin Lakes, NJ, USA) and the results were analyzed using the Beckman Coulter Kaluza analysis software (Beckman Coulter Inc., Brea, CA, USA).
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionJul 2016
- Study completionJul 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type II Diabetes MellitusStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aristidis Veves, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01969084
- Sponsor's protocol ID
- 2013P-000057
- Other IDs
- IIS trial 1218.137
- Status last verified
- Nov 2016
- First submitted
- 29 Aug 2013
- Last updated
- 18 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Baltzis D, Dushay JR, Loader J, Wu J, Greenman RL, Roustit M, Veves A. Effect of Linagliptin on Vascular Function: A Randomized, Placebo-controlled Study. J Clin Endocrinol Metab. 2016 Nov;101(11):4205-4213. doi: 10.1210/jc.2016-2655. Epub 2016 Sep 1.
PubMed 27583476
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Linagliptin on Mitochondrial and Endothelial Function
- ClinicalTrials.gov ID
- NCT01969084
- Acronym / sponsor ID
- 2013P-000057
- Conditions
- Type II Diabetes Mellitus
- Keywords
- Type II Diabetes Mellitus, Diabetes, Metabolism, Linagliptin, Tradjenta, Glucose
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- Jul 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 25 Oct 2013 (estimated)
- Results
- Posted 18 Nov 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators propose to examine the effect of 12 weeks of Linagliptin, a diabetes drug, treatment on inflammation as well as vascular and mitochondrial function in diabetic patients. Investigators hypothesize that Linagliptin will reduce the proinflammatory state, improve endothelial function, increase the blood flow at the muscle microcirculation level and improve mitochondrial function. In this study, investigators will perform tests that evaluate the function of small and large blood vessels by employing ultrasound and laser doppler techniques. In addition MRI scans that evaluate the mitochondrial function of the lower extremity muscles at rest and during exercise will also be employed. Forty subjects with Type 2 diabetes will be studied for twelve weeks and half of them will be randomly assigned to receive linagliptin while the other half will receive placebo. All tests will be performed at the beginning and the end of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Linagliptin | Experimental | Drug: Linagliptin, Other: Microcirculation testing, Other: Macrocirculation testing, Other: MRI ScansSubjects given Linagliptin |
| Sugar pill | Placebo comparator | Drug: Placebo, Other: Microcirculation testing, Other: Macrocirculation testing, Other: MRI ScansSubjects given sugar pill/placebo |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with T2DM whose medical or lifestyle treatment regimen is stable and not expected to be changed during the study period. Patients will be considered stable on their treatment regimen if there have not been any changes in the type of their antidiabetic medications over the past 3 months and/or there have not been any changes in their blood glucose levels that have caused them to see their health care provider more often than usual over the preceding three months. The diagnosis of T2DM will be according to the American Diabetes Association criteria. Subjects previously diagnosed with T2DM will not require confirmatory testing.
- Age 30-70 years
- Patients on insulin should be on a stable insulin regimen for at least 4 months prior to enrollment.
- Patients on antidiabetic treatment will be eligible if they are stable and no change in their treatment is planned for the next three months while they are in the study.
- HBA1c ≤ 10.0
Key exclusion criteria (35 listed)
- Patient with unstable diabetes that has resulted in hyperosmolar coma, DKA, and/or documented increase or decrease in HbA1c of more than 2.0% within the previous 6 months
- Treatment with DPP4 Inhibitors or GLP-1 agonists. Patients who discontinued such treatment should be at least free for a 3-month period.
- Severe proliferative retinopathy that renders the subject legally blinded
- Previously intermittent claudication or diagnosed severe peripheral arterial disease requiring intervention.
- History of Deep Vein Thrombosis (DVT) within the past 3 months.
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 |
|---|---|---|
| LinagliptinAlso: Tradjenta | Drug | Linagliptin |
| Placebo | Drug | Sugar pill |
| Microcirculation testingThe endothelial function of the micro-circulation will be assessed by measuring the hyperemic response of the vessels in the superficial skin of the forearm after the iontophoresis of acetylcholine. The endothelium independent vasodilation will be assessed by the iontophoresis of sodium nitroprusside. Laser Doppler perfusion imaging will be used to measure relative changes in flow velocity.Visible and NIR Medical Hyperspectral Imaging (MHSI) data will be collected with a HyperMed OxyView MHSI System (HyperMed, Inc., Watertown, MA). MHSI images will be obtained from same forearm area where the iontophoresis of acetylcholine and sodium nitroprusside will be performed, before and after the iontophoresis test. | Other | Linagliptin, Sugar pill |
| Macrocirculation testingUse ultrasound to measure brachial artery flow mediated vasodilation (FMD, endothelium-dependent vasodilation) and nitroglycerin induced dilation (NID, endothelium-independent vasodilation). | Other | Linagliptin, Sugar pill |
| MRI ScansPhosphorus-31 MRI data will be obtained during an exercise protocol. Muscle oxygenation will be measured using the blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI) technique after induced hyperemia. | Other | Linagliptin, Sugar pill |
Primary outcome
Phosphocreatine (PCR) Recovery Time After Exhaustive or up to 6 Minutes of Leg Exercise.
Time frame: Baseline and 12 weeks
Change in the time to phosphocreatine recovery between the baseline visit and post-treatment visit following the graded exercise test.
4 secondary outcomes
Change in Muscle Oxygenation Recovery Time
Time frame: Baseline and 12 weeks
Changes in Vascular Reactivity in the Micro- and Macro-circulation.
Time frame: Baseline and 12 weeks
Changes in SDF1-α and Substance P
Time frame: Baseline and 12 weeks
Changes in Circulating Endothelial Progenitor Cell Phenotypes
Time frame: Baseline and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27583476Baltzis D, Dushay JR, Loader J, Wu J, Greenman RL, Roustit M, Veves A. Effect of Linagliptin on Vascular Function: A Randomized, Placebo-controlled Study. J Clin Endocrinol Metab. 2016 Nov;101(11):4205-4213. doi: 10.1210/jc.2016-2655. Epub 2016 Sep 1.
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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.
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 Phase 4 study testing Linagliptin, Microcirculation testing and Macrocirculation testing in people with Type II Diabetes Mellitus, run by Beth Israel Deaconess 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 5 inclusion and 35 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 18 Nov 2016. 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.
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?
Yes. Results are posted in the registry (first posted 18 Nov 2016). 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?
Phosphocreatine (PCR) Recovery Time After Exhaustive or up to 6 Minutes of Leg Exercise. (time frame: Baseline and 12 weeks). 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 NCT01969084, 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 18 Nov 2016.