DiabetesPhase 4NCT01562678
Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI
A Phase 4 study testing Liraglutide in people with Diabetes and Effects of Liraglutide Administration on Brain Activity, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
The main purpose of this study is to help us understand the effects of diabetes medication Liraglutide on weight loss and hunger. The investigators have already determined what the highest tolerated dose of Liraglutide is through earlier human research studies. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes, Effects of Liraglutide Administration on Brain Activity, Weight Loss
- What is being tested?
- Liraglutide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2012to May 2014
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will be men and women between the ages of 18 and 65. The following table list inclusion criteria for each group (lean diabetic and obese diabetic). Subjects must meet either HbA1c or fasting plasma glucose (FPG) criteria.
- Lean diabetic:
- BMI: 18-25 kg/m2 HbA1c: < 8.9% Fasting plasma glucose: <250 mg/dL Other inclusion criteria: On dietary modification and/or metformin
- Obese diabetic:
- BMI: >27 kg/m2 HbA1c: < 8.9% Fasting plasma glucose: <250 mg/dL Other inclusion criteria: On dietary modification and/or metformin
- Additionally, women participants must use double barrier methods to prevent pregnancy (diaphragm with intravaginal spermicide, cervical cap, male or female condom with spermicide). If a woman suspects that she has become pregnant at any time or does not use one of the contraceptive methods recommended by the investigator, she must notify the study staff. If a woman becomes pregnant, she will be withdrawn from the study. The study staff will follow the progress of her pregnancy and the birth of her child.
Who cannot join
- Uncontrolled diabetes (HbA1c>8.9%, or FPG>250 mg/dL)
- Women who are breastfeeding, pregnant, or wanting to become pregnant.
- Women using IUD
- Any change in the dosage of hormonal contraceptive medications (birth control pills, implanon). Subjects should remain on same medication/ same dose during the time of the entire study.
- Moderate (creatinine clearance of 30-59 ml/min) and severe renal impairment (creatinine clearance below 30 ml/min) and end-stage renal disease
- Moderate, or severe hepatic impairment
Show all 38Show fewer
- Hypersensitivity to the active substance or any of the excipients in liraglutide
- History of diabetic ketoacidosis
- Congestive heart failure
- Inflammatory conditions like inflammatory bowel disease, Rheumatoid arthritis etc
- Gastroparesis
- Pancreatitis
- Gallstones- as they may cause increased risk of pancreatitis
- Alcohol consumption- the maximum quantity for men is 140g-210g per week. For women, the range is 84g-140g per week or drinking as consuming no more than two drinks a day for men and one for women. Alcohol can cause increased risk of pancreatitis and hypoglycemia.
- Untreated thyroid disease like hypothyroidism or hyperthyroidism
- Subjects taking the following medications: warfarin, steroids (inhaled or systemic due to reduced hypoglycemic effect), and subjects on other hormones (LHRH analogs etc).
- Subjects on any oral anti-diabetic agent except metformin
- Personal or family history of MEN II or medullary thyroid cancer
- Subjects with any type of bioimplant activated by mechanical, electronic, or magnetic means (e.g. cochlear implants, pacemakers, neuron or biostimulators, electronic infusion pumps, etc.)
- Subjects with any type of metallic implant that could potentially be displaced or damaged during MRI, such as aneurysm clips, metallic skull plates, surgical implants etc. or metal containing tattoos
- Anxiety and/or claustrophobia
- Uncontrolled cardiac impairment, circulatory impairment, or inability to perspire (poor thermoregulatory function)
- Significant sensory or motor impairment
- Epilepsy, particularly photo-sensitive epilepsy, which may place the individual at a higher risk for adverse events during fMRI scanning with visual stimulation
- Subjects with neurological problems which may interfere with or complicate testing (e.g. presence of titubation)
- Body weight above the limitation of the MRI scanning table (330lbs/150 Kg) or body dimensions that could difficult the performance of the scan.
- Subjects who cannot adhere to the experimental protocol for any reason
- Anemia with Hgb less than 10
- Uncontrolled infectious diseases (e.g. HIV, hepatitis, chronic infections etc)
- Any uncontrolled endocrine condition, e.g Cushing's, Acromegaly, etc
- Any cancers or lymphoma
- Eating disorders like anorexia, bulimia
- Severe hypertriglyceridemia (triglycerides >500 mg/dl)
- Weight loss surgery or gastrectomy
- Any changes in medications that affect brain function, e.g. anti-depressants, anti-psychotics, anti-anxiety, anti-seizure medications, antihypertensives etc (subjects should remain on same medication/ same dose during the time of the entire study).
- Irregular periods, defined as cycle length less than 22 days or more than 40 days.
- Any change in smoking status.
- Vegetarians- as food images presented will include numerous non-vegetarian items and thus will not be appealing as high calorie food items.
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
About this study
The main purpose of this study is to help us understand the effects of diabetes medication Liraglutide on weight loss and hunger. The investigators have already determined what the highest tolerated dose of Liraglutide is through earlier human research studies. Liraglutide was approved by the FDA in January 2010 for treatment of diabetes.
The investigators will also study the following:
- The impact of Liraglutide on brain responses to food
- It's effect on physiological and mental performance
- If its effect on the brain differs among obese and lean diabetic subjects.
Read the detailed description
This is a randomized, placebo controlled, cross-over, double-blinded study to assess the effects of liraglutide on brain activation in areas involved in cognitive control and reward during food visualization.
Study participation will span approximately 1.5-2 months. Subjects will learn to self-administer the medication and will have a total of 8 study visits plus one screening visit. The visits will include the following tests/procedures:
- Vital signs (blood pressure, temperature, heart rate, breathing rate)
- Height, weight and other body measurements like waist
- Blood tests
- Urine pregnancy test (women only)
- Electrocardiogram (EKG)
- Medical history
- Physical exam
- Body Composition tests
- Study logs to record food intake and blood sugar
- functional MRI
We plan to recruit a total of 24 subjects to be treated with placebo and liraglutide. We propose to enroll 12 obese diabetic (type 2) and 12 lean diabetic (type 2) subjects. Equal numbers of men and women will be enrolled and the randomization will block for gender.
- Being tested
- Liraglutide, Placebo
- Keywords
- fMRI, Liraglutide, diabetes, GLP-1
- Medical subject headings
- Diabetes Mellitus, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LiraglutideDrug
Also called victoza
In the experimental arm of this randomized, placebo controlled, cross-over, double-blinded study to assess the effects of liraglutide. Subjects will self-inject Liraglutide once per day for 18 days. Subjects will start the treatment with a dose of 0.6 mg for the first week, then 1.2 mg for the second week and 1.8 mg for 3 days in the third week.
PlaceboDrug
In the placebo arm of this randomized, placebo controlled, cross-over, double-blinded study to assess the effects of liraglutide. Subjects will self-inject placebo once per day for 18 days.
| Study group | Role | What they receive |
|---|---|---|
| Liraglutide | Experimental | Not described Receives: Drug: Liraglutide |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change Between Highly Desirable vs. Less Desirable Food Cues in the Effect Size of Cortical Activation During Food Visualization
Effect size (region of interest z-scores, derived from z-maps of the brain) shown below is the difference in parietal cortex activation to highly desirable (high fat or high calorie, e.g. cakes, pies, fries) versus less desirable (low fat or low calorie, e.g. vegetables, fruits) food cues for each treatment condition (liraglutide or placebo) at the end of the treatment period.
Measured: 18 days of Liraglutide or placebo treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionMay 2014
- Study completionMay 2014
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 (2)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess 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
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christos Mantzoros, Beth Israel Deaconess Medical Center
- Investigators
- Christos Mantzoros, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01562678
- Sponsor's protocol ID
- 2011P000280
- Status last verified
- Apr 2017
- First submitted
- 22 Mar 2012
- Last updated
- 31 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Angelidi AM, Kokkinos A, Sanoudou D, Connelly MA, Alexandrou A, Mingrone G, Mantzoros CS. Early metabolomic, lipid and lipoprotein changes in response to medical and surgical therapeutic approaches to obesity. Metabolism. 2023 Jan;138:155346. doi: 10.1016/j.metabol.2022.155346. Epub 2022 Nov 12.
PubMed 36375643Farr OM, Sofopoulos M, Tsoukas MA, Dincer F, Thakkar B, Sahin-Efe A, Filippaios A, Bowers J, Srnka A, Gavrieli A, Ko BJ, Liakou C, Kanyuch N, Tseleni-Balafouta S, Mantzoros CS. GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial. Diabetologia. 2016 May;59(5):954-65. doi: 10.1007/s00125-016-3874-y. Epub 2016 Feb 1.
PubMed 26831302
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRI
- ClinicalTrials.gov ID
- NCT01562678
- Acronym / sponsor ID
- 2011P000280
- Keywords
- fMRI, Liraglutide, diabetes, GLP-1
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Study start
- Mar 2012
- Primary completion
- May 2014 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 26 Mar 2012 (estimated)
- Results
- Posted 31 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of this study is to help us understand the effects of diabetes medication Liraglutide on weight loss and hunger. The investigators have already determined what the highest tolerated dose of Liraglutide is through earlier human research studies. Liraglutide was approved by the FDA in January 2010 for treatment of diabetes.
The investigators will also study the following:
- The impact of Liraglutide on brain responses to food
- It's effect on physiological and mental performance
- If its effect on the brain differs among obese and lean diabetic subjects.
Detailed description
This is a randomized, placebo controlled, cross-over, double-blinded study to assess the effects of liraglutide on brain activation in areas involved in cognitive control and reward during food visualization.
Study participation will span approximately 1.5-2 months. Subjects will learn to self-administer the medication and will have a total of 8 study visits plus one screening visit. The visits will include the following tests/procedures:
- Vital signs (blood pressure, temperature, heart rate, breathing rate)
- Height, weight and other body measurements like waist
- Blood tests
- Urine pregnancy test (women only)
- Electrocardiogram (EKG)
- Medical history
- Physical exam
- Body Composition tests
- Study logs to record food intake and blood sugar
- functional MRI
We plan to recruit a total of 24 subjects to be treated with placebo and liraglutide. We propose to enroll 12 obese diabetic (type 2) and 12 lean diabetic (type 2) subjects. Equal numbers of men and women will be enrolled and the randomization will block for gender.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liraglutide | Experimental | Drug: Liraglutide |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subjects will be men and women between the ages of 18 and 65. The following table list inclusion criteria for each group (lean diabetic and obese diabetic). Subjects must meet either HbA1c or fasting plasma glucose (FPG) criteria.
- BMI: 18-25 kg/m2 HbA1c: < 8.9% Fasting plasma glucose: <250 mg/dL Other inclusion criteria: On dietary modification and/or metformin
- BMI: >27 kg/m2 HbA1c: < 8.9% Fasting plasma glucose: <250 mg/dL Other inclusion criteria: On dietary modification and/or metformin
- Additionally, women participants must use double barrier methods to prevent pregnancy (diaphragm with intravaginal spermicide, cervical cap, male or female condom with spermicide). If a woman suspects that she has become pregnant at any time or does not use one of the contraceptive methods recommended by the investigator, she must notify the study staff. If a woman becomes pregnant, she will be withdrawn from the study. The study staff will follow the progress of her pregnancy and the birth of her child.
Key exclusion criteria (38 listed)
- Uncontrolled diabetes (HbA1c>8.9%, or FPG>250 mg/dL)
- Women who are breastfeeding, pregnant, or wanting to become pregnant.
- Women using IUD
- Any change in the dosage of hormonal contraceptive medications (birth control pills, implanon). Subjects should remain on same medication/ same dose during the time of the entire study.
- Moderate (creatinine clearance of 30-59 ml/min) and severe renal impairment (creatinine clearance below 30 ml/min) and end-stage renal disease
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: victozaIn the experimental arm of this randomized, placebo controlled, cross-over, double-blinded study to assess the effects of liraglutide. Subjects will self-inject Liraglutide once per day for 18 days. Subjects will start the treatment with a dose of 0.6 mg for the first week, then 1.2 mg for the second week and 1.8 mg for 3 days in the third week. | Drug | Liraglutide |
| PlaceboIn the placebo arm of this randomized, placebo controlled, cross-over, double-blinded study to assess the effects of liraglutide. Subjects will self-inject placebo once per day for 18 days. | Drug | Placebo |
Primary outcome
Change Between Highly Desirable vs. Less Desirable Food Cues in the Effect Size of Cortical Activation During Food Visualization
Time frame: 18 days of Liraglutide or placebo treatment
Effect size (region of interest z-scores, derived from z-maps of the brain) shown below is the difference in parietal cortex activation to highly desirable (high fat or high calorie, e.g. cakes, pies, fries) versus less desirable (low fat or low calorie, e.g. vegetables, fruits) food cues for each treatment condition (liraglutide or placebo) at the end of the treatment period.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36375643Angelidi AM, Kokkinos A, Sanoudou D, Connelly MA, Alexandrou A, Mingrone G, Mantzoros CS. Early metabolomic, lipid and lipoprotein changes in response to medical and surgical therapeutic approaches to obesity. Metabolism. 2023 Jan;138:155346. doi: 10.1016/j.metabol.2022.155346. Epub 2022 Nov 12.
- Derived from this study: PubMed 26831302Farr OM, Sofopoulos M, Tsoukas MA, Dincer F, Thakkar B, Sahin-Efe A, Filippaios A, Bowers J, Srnka A, Gavrieli A, Ko BJ, Liakou C, Kanyuch N, Tseleni-Balafouta S, Mantzoros CS. GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial. Diabetologia. 2016 May;59(5):954-65. doi: 10.1007/s00125-016-3874-y. Epub 2016 Feb 1.
- Mantzoros Lab WebsiteLink provided by the sponsor.
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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.
Christos Mantzoros, MD principal investigator
Beth Israel Deaconess 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 Diabetes and Effects of Liraglutide Administration on Brain Activity, 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 6 inclusion and 38 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 31 May 2017. 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 31 May 2017). 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?
Change Between Highly Desirable vs. Less Desirable Food Cues in the Effect Size of Cortical Activation During Food Visualization (time frame: 18 days of Liraglutide or placebo treatment). 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 NCT01562678, which also lists 2 linked publications.
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 31 May 2017.