Autonomic Nervous System DiseasesPhase 2NCT03426085
The Effects of Liraglutide on Sudomotor Function and Inflammation in Type 2 Diabetes
A Phase 2 study testing Liraglutide 6 mg Solution for Injection in people with Autonomic Nervous System Diseases and Sweat Gland Diseases, run by Eastern Virginia Medical School at 1 site in United States.
Trial summary
The purpose of this study is to conduct an interventional, one year, randomized, double blind, placebo-controlled trial with Liraglutide in patients with type 2 diabetes (diabetes duration of >6 months and <10 years, HbA1c <10%) to evaluate its effects on the peripheral autonomic nervous system, as well as… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Autonomic Nervous System Diseases, Sweat Gland Diseases, Diabetic Neuropathy With Neurologic Complication
- What is being tested?
- Liraglutide 6 mg Solution for Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- May 2016to Aug 2020
- Phase
- Phase 2
- 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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- established type 2 diabetes (diabetes duration of >6 months and <10 years).
- Age 18-80 years
- HbA1c at screening ≤ 10%
- Subjects on stable (≥3 months prior to Screening) Standard of Care background diabetic therapy. Diabetic treatment regimens include diet and exercise alone or in association with oral anti-diabetic drugs (monotherapy or combinations) and/or long-acting insulin.
Who cannot join
- Presence of type 1 diabetes mellitus (defined as C-peptide <1 ng /ml, <35y and prone to ketoacidosis)
- Treatment with rapid-acting or short-acting insulin within the last 3 months
- Proliferative retinopathy or maculopathy requiring acute treatment
- Impaired renal function , defined as serum creatinine ≥ 125 µmol/L (≥1.4 mg/dL) for males and ≥ 110 µmol/L (≥1.24 mg/dL) for females
- Impaired liver function, defined as aspartate transaminase (AST) or alanine transaminase (ALT), ≥ 2.5 times the upper limit of normal
- Presence of clinically significant peripheral or autonomic neuropathy that is clearly of non-diabetic origin
Show all 30Show fewer
- Uncontrolled treated/untreated hypertension (systolic blood pressure (BP) ≥180 or diastolic blood pressure (BP) ≥100 at screening)
- Clinically significant active macrovascular disease including myocardial infarction or cerebrovascular event within the past 6 months. Other exclusions include coronary artery bypass graft or coronary angioplasty in the previous 3 months, unstable angina pectoris (chest pain at rest, worsening chest pain, or admission to the emergency room (ER) or hospital for chest pain) within the previous 3 months, and/or congestive heart failure (NYHA Class III-IV)
- Subjects known to be Hepatitis B surface antigen or Hepatitis C antibody positive with active hepatitis.
- Active infection (e.g., human immunodeficiency virus (HIV), hepatitis), or a history of severe infection during the 30 days prior to screening
- Evidence of immunocompromised status, including but not limited to individuals who have undergone organ transplantation, who are known to be HIV positive, or who are taking immunosuppressive drugs or chronic systemic corticosteroid treatment.
- Major surgical procedure during the 30 days prior to screening
- Diagnosis and/or treatment of malignancy (except for basal cell or squamous cell skin cancer, in-situ carcinoma of the cervix, or in-situ prostate cancer) within the past 5 years
- Known clinically significant gastric emptying abnormality (e.g. severe gastroparesis), or history of gastric bypass (bariatric) surgery
- Thyroid stimulating hormone (TSH) outside of normal limits at screening, or presence of a thyroid nodule detected on physical examination that has not been fully evaluated
- Thyroid hormone therapy that has not been stable for ≥6 weeks prior to Screening
- Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 (MEN-2)
- History of acute or chronic pancreatitis
- Subjects taking medications that are known to affect autonomic function need to be at a stable dose of those medications ≥ 3 months prior to inclusion in the study
- Other clinically significant, active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, genitourinary or hematological system that, in the opinion of the investigator, would compromise the subject's participation in the study, might confound the results of the study or pose additional risk in administering the study drug
- Recurrent severe hypoglycemia and/or hypoglycemia unawareness.
- Concurrent participation in another clinical trial with use of an experimental drug or device within 30 days of study entry.
- Known or suspected history of alcohol or substance abuse
- Mental incapacity, unwillingness or language barrier precluding adequate understanding of or cooperation with the study.
- Women of childbearing potential (WOCBP*) who are pregnant, breast-feeding or intend to become pregnant
- WOCBP* must have a negative pregnancy test at Screening and must agree to use adequate contraceptive methods** during the study and for one additional menstrual cycle following the end-of-treatment visit
- Known or suspected hypersensitivity to study product(s) or related products
- Patients with low vitamin B12 levels will be excluded
- Current use or use 6 months prior to study participation of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon like peptide-1 (GLP-1) agonists will be excluded
- Liraglutide has not been studied in combination with prandial insulin. Patients who use prandial insulin may be excluded
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Strelitz Diabetes Center
Norfolk, Virginia, 23510
Henri K Parson, PhD, 757-446-7976, parsonhk@evms.edu
Joshua F Edwards, MPH, 7574460335, edwardj@evms.edu
About this study
The purpose of this study is to conduct an interventional, one year, randomized, double blind, placebo-controlled trial with Liraglutide in patients with type 2 diabetes (diabetes duration of >6 months and <10 years, HbA1c <10%) to evaluate its effects on the peripheral autonomic nervous system, as well as inflammatory markers, and measures of oxidative and nitrosative stress.
Read the detailed description
The investigators propose to examine the effects of GLP-1 receptor agonist Liraglutide on autonomic sudomotor function and endothelial and neurovascular functions as well as markers of inflammation in patients with type 2 diabetes mellitus (T2DM). The primary objective will be changes in peripheral autonomic function using sudorimetry (Sudoscan) after 1 year of treatment.
The secondary objectives include changes on markers of inflammation and oxidative/nitrosative stress including C-reactive protein (CRP), interleukin 1 beta (IL-1β), Interleukin 6 (IL6), interleukin 12 (IL12), interleukin 10 (IL10), tumor necrosis factor α (TNF α), plasminogen activator Inhibitor 1 (PAI-1), superoxide dismutase (SOD), nitrotyrosine, carboxymethyl-lysine (CML), thiobarbituric acid reactive substances (TBARS), and asymmetric dimethylarginine (ADMA). Additional objectives include changes in neurovascular and endothelial function, measured by continuous Laser Doppler assessment of skin blood flow in response to different stimuli; and changes in sensory-motor peripheral nerve function, measured by clinical neuropathy scores (NSS \& NIS), quantitative sensory testing and nerve conduction testing.
The aim of this study is to capture patients early in the disease process, when autonomic dysfunction is still potentially reversible. Several studies have shown the presence of autonomic imbalance in the early stages of diabetes and even in the pre-diabetic state (impaired glucose tolerance, impaired fasting glucose, and metabolic syndrome). We hypothesize that by treating type 2 diabetic patients with Liraglutide early in the disease process (<10 years of diagnosis), we will be able to improve peripheral autonomic imbalance, endothelial and neurovascular function, and reduce inflammation and oxidative/nitrosative stress. This will shed further insight into the mechanisms by which glucagon-like peptide-1 (GLP-1) exerts a neuroprotective role and improves the inflammatory process. The possibility of improving autonomic imbalance, endothelial function and inflammation may have important impact in the development of new potential therapeutic strategies to abrogate the microvascular complications of diabetes
- Conditions
- Autonomic Nervous System Diseases, Sweat Gland Diseases, Diabetic Neuropathy With Neurologic Complication
- Being tested
- Liraglutide 6 mg Solution for Injection, Placebo
- Medical subject headings
- Autonomic Nervous System Diseases, Sweat Gland Diseases, Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liraglutide 6 mg Solution for InjectionDrug
PlaceboOther
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Same formulation as active medication minus the active ingredient. Patients will start with 0.1 mL of liraglutide placebo and will escalate the dose every week in 0.1 ml increments until the 0.3 ml dose is reached. Escalation will be done according to patients' tolerance and glucose control Receives: Other: Placebo |
| Liraglutide 6 mg Solution for Injection | Experimental | After randomization, patients will undergo a treatment dose escalation phase. Liraglutide will be started at 0.6 mg SQ QD for 1 week, increased to 1.2 mg subcutaneous, per day (SQ, QD) for 1 week, and then increased and maintained on 1.8 mg SQ QD or maximally tolerated dose if self monitored blood glucose (SMBG) is at goal. Escalation will be done according to patients' tolerance and glucose control Receives: Drug: Liraglutide 6 mg Solution for Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sudomotor Function
Changes in peripheral autonomic function using sudorimetry (Sudoscan) after 1 year of treatment.
Measured: One Year
Secondary outcomes (4)
Inflammatory Markers C-Reactive Protein (CRP)
Changes on markers of inflammation and oxidative/nitrosative stress including C-reactive protein (CRP)
Measured: One year
Inflammatory Markers IL-1β
Changes on markers of inflammation and oxidative/nitrosative stress including IL-1β
Measured: One Year
Inflammatory Markers IL6
Changes on markers of inflammation and oxidative/nitrosative stress including IL6
Measured: One Year
Inflammatory Markers Tumor Necrosis factor α (TNF α)
Changes on markers of inflammation and oxidative/nitrosative stress including Tumor Necrosis factor α (TNF α)
Measured: One Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2018
- Study startMay 2016
- Primary completionApr 2020 (estimated)
- Study completionAug 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Autonomic Nervous System DiseasesStudies 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eastern Virginia Medical School
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aaron I. Vinik, MD, PhD, Eastern Virginia Medical School
- Investigators
- Aaron Vinik, MD, PhD, Principal investigator, Eastern Virginia Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03426085
- Sponsor's protocol ID
- 15-12-FB-0218
- Status last verified
- Feb 2019
- First submitted
- 2 Feb 2018
- Last updated
- 11 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Liraglutide on Sudomotor Function and Inflammation in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT03426085
- Acronym / sponsor ID
- 15-12-FB-0218
- Conditions
- Autonomic Nervous System Diseases, Sweat Gland Diseases, Diabetic Neuropathy With Neurologic Complication
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Eastern Virginia Medical SchoolUniversity, hospital or other
- Study start
- May 2016
- Primary completion
- Apr 2020 (estimated)
- Study completion
- Aug 2020 (estimated)
- First posted
- 8 Feb 2018 (actual)
- 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.
The purpose of this study is to conduct an interventional, one year, randomized, double blind, placebo-controlled trial with Liraglutide in patients with type 2 diabetes (diabetes duration of >6 months and <10 years, HbA1c <10%) to evaluate its effects on the peripheral autonomic nervous system, as well as inflammatory markers, and measures of oxidative and nitrosative stress.
Detailed description
The investigators propose to examine the effects of GLP-1 receptor agonist Liraglutide on autonomic sudomotor function and endothelial and neurovascular functions as well as markers of inflammation in patients with type 2 diabetes mellitus (T2DM). The primary objective will be changes in peripheral autonomic function using sudorimetry (Sudoscan) after 1 year of treatment.
The secondary objectives include changes on markers of inflammation and oxidative/nitrosative stress including C-reactive protein (CRP), interleukin 1 beta (IL-1β), Interleukin 6 (IL6), interleukin 12 (IL12), interleukin 10 (IL10), tumor necrosis factor α (TNF α), plasminogen activator Inhibitor 1 (PAI-1), superoxide dismutase (SOD), nitrotyrosine, carboxymethyl-lysine (CML), thiobarbituric acid reactive substances (TBARS), and asymmetric dimethylarginine (ADMA). Additional objectives include changes in neurovascular and endothelial function, measured by continuous Laser Doppler assessment of skin blood flow in response to different stimuli; and changes in sensory-motor peripheral nerve function, measured by clinical neuropathy scores (NSS \& NIS), quantitative sensory testing and nerve conduction testing.
The aim of this study is to capture patients early in the disease process, when autonomic dysfunction is still potentially reversible. Several studies have shown the presence of autonomic imbalance in the early stages of diabetes and even in the pre-diabetic state (impaired glucose tolerance, impaired fasting glucose, and metabolic syndrome). We hypothesize that by treating type 2 diabetic patients with Liraglutide early in the disease process (<10 years of diagnosis), we will be able to improve peripheral autonomic imbalance, endothelial and neurovascular function, and reduce inflammation and oxidative/nitrosative stress. This will shed further insight into the mechanisms by which glucagon-like peptide-1 (GLP-1) exerts a neuroprotective role and improves the inflammatory process. The possibility of improving autonomic imbalance, endothelial function and inflammation may have important impact in the development of new potential therapeutic strategies to abrogate the microvascular complications of diabetes
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: PlaceboSame formulation as active medication minus the active ingredient. Patients will start with 0.1 mL of liraglutide placebo and will escalate the dose every week in 0.1 ml increments until the 0.3 ml dose is reached. Escalation will be done according to patients' tolerance and glucose control |
| Liraglutide 6 mg Solution for Injection | Experimental | Drug: Liraglutide 6 mg Solution for InjectionAfter randomization, patients will undergo a treatment dose escalation phase. Liraglutide will be started at 0.6 mg SQ QD for 1 week, increased to 1.2 mg subcutaneous, per day (SQ, QD) for 1 week, and then increased and maintained on 1.8 mg SQ QD or maximally tolerated dose if self monitored blood glucose (SMBG) is at goal. Escalation will be done according to patients' tolerance and glucose control |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- established type 2 diabetes (diabetes duration of >6 months and <10 years).
- Age 18-80 years
- HbA1c at screening ≤ 10%
- Subjects on stable (≥3 months prior to Screening) Standard of Care background diabetic therapy. Diabetic treatment regimens include diet and exercise alone or in association with oral anti-diabetic drugs (monotherapy or combinations) and/or long-acting insulin.
Key exclusion criteria (30 listed)
- Presence of type 1 diabetes mellitus (defined as C-peptide <1 ng /ml, <35y and prone to ketoacidosis)
- Treatment with rapid-acting or short-acting insulin within the last 3 months
- Proliferative retinopathy or maculopathy requiring acute treatment
- Impaired renal function , defined as serum creatinine ≥ 125 µmol/L (≥1.4 mg/dL) for males and ≥ 110 µmol/L (≥1.24 mg/dL) for females
- Impaired liver function, defined as aspartate transaminase (AST) or alanine transaminase (ALT), ≥ 2.5 times the upper limit of normal
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 |
|---|---|---|
| Liraglutide 6 mg Solution for Injection | Drug | Liraglutide 6 mg Solution for Injection |
| Placebo | Other | Placebo |
Primary outcome
Sudomotor Function
Time frame: One Year
Changes in peripheral autonomic function using sudorimetry (Sudoscan) after 1 year of treatment.
4 secondary outcomes
Inflammatory Markers C-Reactive Protein (CRP)
Time frame: One year
Inflammatory Markers IL-1β
Time frame: One Year
Inflammatory Markers IL6
Time frame: One Year
Inflammatory Markers Tumor Necrosis factor α (TNF α)
Time frame: One Year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 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.
Aaron Vinik, MD, PhD principal investigator
Eastern Virginia Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Liraglutide 6 mg Solution for Injection in people with Autonomic Nervous System Diseases and Sweat Gland Diseases, run by Eastern Virginia Medical School 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 30 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: status not confirmed, as of the sponsor's last update on 11 Feb 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Henri K Parson, PhD (7574467976, parsonhk@evms.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sudomotor Function (time frame: One Year). 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 11 Feb 2019.