Neural Development, Obesity, Childhood
Conditions
Brief summary
To study the effects of liraglutide on neural responses to high fructose corn syrup (HFCS) in individuals with obesity.
Detailed description
Adolescents are the highest consumers of sugar sweetened beverages (SSB) potentially because their developing brains are most susceptible to the rewarding neural effects of sugar consumption. Thus, we specifically target this population (adolescents) to understand neural mechanisms involved in excess sugar consumption which predisposes to the development of obesity, prediabetes, and type 2 diabetes. Upon results entry, the data elements in protocol section of this record were updated to reflect the appropriate study phase and primary purpose that was inadvertently mischaracterized at the time of registration. One of the secondary outcomes was removed because it was a duplicate of the second primary outcome.
Interventions
DRUGLiraglutide
Liraglutide will be supplied in the following package sizes containing disposable, pre-filled, multidose pens. Each individual pen delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg (6 mg/mL, 3 mL). Liraglutide will be self-administered daily for 12 weeks under the following regimen: 0.6mg for 1 week, 1.2mg for 1 week, 1.8mg for 1 week, 2.4mg for 1 week, 3.0mg until week 12.
Sponsors
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Intervention model description
15 control and 30 obese subjects
Eligibility
Sex/Gender
ALL
Age
18 Years to 39 Years
Healthy volunteers
Yes
Inclusion criteria
1. 18-39 years old 2. Lean (BMI 18.5-24.9 kg/m2) with normoglycemia 3. Obese (BMI 30-45 kg/m2) with or without prediabetes 4. Weight stable 5. Right handed 6. Able to read and write in English 7. Able to provide written and verbal informed consent
Exclusion criteria
1. Current active participation in a weight loss program or weight loss of \>=10% of total body weight during the previous 6 months 2. Prior bariatric surgery or current gastric balloon 3. Weight \>440lbs or waist circumference \>142cm 4. Following a vegetarian/vegan diet or dieting/restricting food 5. Significant medical condition 6. Current use of weight-loss medications or supplements, psychiatric medications or anti- hyperglycemic medications 7. History of or family history of multiple endocrine neoplasia type 1 (MEN-I) or medullary thyroid cancer, alcoholism, or previous history of pancreatitis 8. Females who are pregnant or lactating, or who are unwilling to use proper contraception or remain abstinent, 9. Claustrophobia that would interfere with MRI or metal in their body that would pose a risk in the MRI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages. | 1 week | To investigate brain response (using fMRI) to acute consumption of sugar sweetened beverages in obese prediabetic adolescents/young adults (age 18-39 yrs), increase in cerebral blood flow was monitored in participants as a binary outcome (increase/no increase). |
| Change in Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages. | 1 week and 12 weeks | To investigate brain response (using fMRI) to acute consumption of sugar sweetened drinks in obese prediabetic adolescents/young adults (age 18-39 yrs). Measurement at 1 week was compared to measurement at 12 weeks. Increased blood flow in thalamus was monitored in participants as a binary outcome (increase/no increase). |
Other
| Measure | Time frame | Description |
|---|---|---|
| To Investigate the Role of Specific Metabolic/Hormonal Responses in the Setting of Liraglutide Treatment, in Affecting Neural Responses to Sugar Ingestion. | 1 week and 12 weeks | To investigate the role of specific metabolic/hormonal responses in the setting of liraglutide treatment, in affecting neural responses to sugar ingestion. Metabolic response is represented by the whole-body insulin sensitivity index (WBISI). The Oral Glucose Tolerance Test (OGTT) were performed at Baseline and Week 12. Insulin Sensitivity was measured by obtaining glucose and insulin levels in a fasting state and at 2 hours after administration of oral glucose load. Matsuda index = 10,000/SQRT \[glucose concentration (mg/dL) (fasting)\*insulin concentration (uIU/mL) (fasting)\*glucose concentration (mg/dL) (2 hours after glucose load)\*insulin concentration (uIU/mL) (2 hours after glucose load)\], with higher numbers indicating better insulin sensitivity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Obese Subjects Subjects will self-administer Liraglutide once daily for 12 weeks.
Liraglutide: Liraglutide will be supplied in the following package sizes containing disposable, pre-filled, multidose pens. Each individual pen delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg (6 mg/mL, 3 mL). Liraglutide will be self-administered daily for 12 weeks under the following regimen: 0.6mg for 1 week, 1.2mg for 1 week, 1.8mg for 1 week, 2.4mg for 1 week, 3.0mg until week 12. | 8 |
| Lean Subjects no intervention | 5 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 |
| Overall Study | Could not be scanned or followed up due to COVID | 1 | 0 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | Obese Subjects | Lean Subjects | Total |
|---|---|---|---|
| Age, Continuous | 26 years STANDARD_DEVIATION 5.5 | 21.2 years STANDARD_DEVIATION 1.9 | 24.2 years STANDARD_DEVIATION 5 |
| Race/Ethnicity, Customized African American | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Hispanic | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 1 Participants | 3 Participants |
| Region of Enrollment United States | 8 participants | 5 participants | 13 participants |
| Sex: Female, Male Female | 7 Participants | 3 Participants | 10 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
| Years of Education | 14 years STANDARD_DEVIATION 2.9 | 15 years STANDARD_DEVIATION 1.8 | 14 years STANDARD_DEVIATION 2.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 5 |
| other Total, other adverse events | 3 / 8 | 0 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 5 |
Outcome results
Primary
Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages.
To investigate brain response (using fMRI) to acute consumption of sugar sweetened beverages in obese prediabetic adolescents/young adults (age 18-39 yrs), increase in cerebral blood flow was monitored in participants as a binary outcome (increase/no increase).
Time frame: 1 week
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Obesity | Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages. | Increase in cerebral blood flow in the caudate, putamen and insula | 8 Participants |
| Participants With Obesity | Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages. | No increase in cerebral blood flow in the caudate, putamen and insula | 0 Participants |
| Participants Who Are Lean | Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages. | Increase in cerebral blood flow in the caudate, putamen and insula | 0 Participants |
| Participants Who Are Lean | Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages. | No increase in cerebral blood flow in the caudate, putamen and insula | 5 Participants |
Primary
Change in Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages.
To investigate brain response (using fMRI) to acute consumption of sugar sweetened drinks in obese prediabetic adolescents/young adults (age 18-39 yrs). Measurement at 1 week was compared to measurement at 12 weeks. Increased blood flow in thalamus was monitored in participants as a binary outcome (increase/no increase).
Time frame: 1 week and 12 weeks
Population: 12 week follow up only took place in participants with obesity in matched cases.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Participants With Obesity | Change in Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages. | Increased blood flow in thalamus at 1 week | 0 Participants |
| Participants With Obesity | Change in Brain Response in Obese Young Adults Who Drink Sugar Sweetened Beverages. | Increased blood flow in thalamus at 12 weeks | 4 Participants |
Other Pre-specified
To Investigate the Role of Specific Metabolic/Hormonal Responses in the Setting of Liraglutide Treatment, in Affecting Neural Responses to Sugar Ingestion.
To investigate the role of specific metabolic/hormonal responses in the setting of liraglutide treatment, in affecting neural responses to sugar ingestion. Metabolic response is represented by the whole-body insulin sensitivity index (WBISI). The Oral Glucose Tolerance Test (OGTT) were performed at Baseline and Week 12. Insulin Sensitivity was measured by obtaining glucose and insulin levels in a fasting state and at 2 hours after administration of oral glucose load. Matsuda index = 10,000/SQRT \[glucose concentration (mg/dL) (fasting)\*insulin concentration (uIU/mL) (fasting)\*glucose concentration (mg/dL) (2 hours after glucose load)\*insulin concentration (uIU/mL) (2 hours after glucose load)\], with higher numbers indicating better insulin sensitivity.
Time frame: 1 week and 12 weeks
Population: 12 week follow up only took place in participants with obesity in matched cases.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants With Obesity | To Investigate the Role of Specific Metabolic/Hormonal Responses in the Setting of Liraglutide Treatment, in Affecting Neural Responses to Sugar Ingestion. | 1 Week | 3.54 Index | Standard Deviation 2.05 |
| Participants With Obesity | To Investigate the Role of Specific Metabolic/Hormonal Responses in the Setting of Liraglutide Treatment, in Affecting Neural Responses to Sugar Ingestion. | 12 Weeks | 4.08 Index | Standard Deviation 3.58 |