ObesityPhase 1NCT01501084
Effects of the GLP-1 Exenatide on Satiety in Lean and Obese Women
A Phase 1 study testing Exenatide and Normal saline .2cc subcutaneous injection in people with Obesity, run by University of California, Los Angeles at 1 site in United States.
Trial summary
Obesity is a major health problem in the US and many Western countries, with more than half of the population being overweight or obese. Yet, despite intense research efforts into the mechanisms underlying obesity and into the development of novel pharmacologic interventions, bariatric surgery, including gastric… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- Exenatide and Normal saline .2cc subcutaneous injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2011to Feb 2013
- Phase
- Phase 1
- 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 40 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- FEMALES 18 to 40 years of age, inclusive
- Lean control subjects with BMI's between 19 and 25kg/m2.
- Obese subjects with BMI's between 30 and 35kg/m2.
- Willingness to participate in this study as evidenced by a signed, written informed consent form (ICF).
- Willingness to avoid pregnancy and practice adequate birth control (abstinence, oral contraception, intrauterine devices, implantable devices, or barrier method with spermicide) during the time of study enrollment.
- Negative urine pregnancy tests at all visits.
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- All subjects must be premenopausal.
- In the follicular stage of the menstrual cycle, as determined by menstrual history at Visit 2 \&3.
- Ambulatory outpatient (not depending exclusively on a wheelchair for mobility)
- English is primary oral and written language.
- Random (non fasting) Blood sugar level < 200mg/dl at screening.
- Right-handed
Who cannot join
- Evidence of structural abnormality of the gastrointestinal tract or GI diseases/conditions. Exclusionary GI conditions include but are not limited to: gastrointestinal surgery (exceptions: appendectomy, benign polypectomy, cholecystectomy), pancreatitis, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), esophagitis (exception: symptom controlled reflux disease), celiac disease, gastrointestinal malignancy or obstruction, functional dyspepsia, peptic ulcer disease, lactose intolerance or any malabsorptive condition.
- Clinical evidence of cardiovascular, respiratory, renal, hepatic, malignancy, hematologic, neurologic (including regular migraines defined as more than 1 migraine per month), psychiatric or any disease that the PI determines may interfere with safe participation in the study.
- Very specifically subjects with any history or symptoms of poor glucose control, osteoporosis, diabetes, thyroid, adrenal or other endocrine disorder.
- Subjects with current psychiatric disorder, or history of such disorder in the past 5 years. This list includes but is not limited to bipolar disorder, alcohol or substance abuse/dependence, suicide attempt or behavior, or presence of anxiety or depression at the time of screening. Poorly controlled anxiety or depression will be determined as a result of MINI + interview by the clinician at screening.
- Current history of chronic pain.
- Use of investigational drugs, products or devices within 28 days prior to screen and through study participation.
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- Subjects with current use of any medications/drugs during the study that affect the central nervous system, gastrointestinal motility, autonomic activity or pain sensation, including but not limited to: opiates or other narcotic analgesics, THC, alpha adrenergic receptor antagonists, beta blockers, Ca+ blockers, prokinetics and sympatholytic agents, or antidepressants.
- Subjects who have used diet aids within the last month.
- Pregnancy, postpartum within 4 months or breast-feeding
- Subjects who smoke more than 5 cigarettes per month.
- Subjects with BMI of less than 20, between 26 and 29 and over 35.
- Subjects with metal implants, dental retainers, large tattoos (e.g. full arm or back) or claustrophobia; making MRI safety not possible.
- Any clinically significant abnormalities from the screening medical history or physical examination.
- Subjects who exercise excessively (more than 8 hours a week on average).
- Postmenopausal women and/or women who have had oophorectomies.
- Any other condition that the investigator believes would jeopardize the safety or rights of the subject or would render the subject unable to comply with the study protocol.
- Subject taking any medications that might interfere or react badly with the GLP-1 agonist: Exenatide
- Subjects with a non-fasting blood glucose level at > 200 dl/ml.
- MRI visits with fasting blood sugar < 65 or 126 mg/dl
- Left handedness
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress
Los Angeles, California, 90095
About this study
Official title: Effects of the GLP-1 Exenatide on Intrinsic Brain Activity in Lean and Obese Women
Obesity is a major health problem in the US and many Western countries, with more than half of the population being overweight or obese. Yet, despite intense research efforts into the mechanisms underlying obesity and into the development of novel pharmacologic interventions, bariatric surgery, including gastric bypass surgery is the only successful treatment for severe obesity. Mimicking one of the effects of bariatric surgery, e.g. the increased secretion of glucagon-like peptide 1 (GLP-1) could be an effective strategy against obesity.
Obese individuals may be more sensitive to the rewarding aspects of food and less responsive to signals from the gut about actual energy needs. Using functional MRI scanning the investigators plan to examine the effect of Exenatide (a GLP-1 analog known to reduce caloric intake and produce weight loss in both obese and lean individuals) on activity within brain regions/networks involved in reward/motivation and in regulation of energy requirements. The investigators expect the peptide to change the balance between desire to eat for pleasure and the need to eat to maintain homeostasis.
Read the detailed description
PRIMARY STUDY OBJECTIVE The proposed study aims to address two important questions regarding the mechanisms underlying the weight loss associated with exenatide. The investigators primary study objective is to determine whether Exenatide changes the resting state activity of the brain, and alters the connectivity between brain regions involved in homeostatic and hedonic brain circuits.
SECONDARY STUDY OBJECTIVE The secondary study objective is to determine if/how these changes differ between lean and obese subjects
SIGNIFICANCE Obesity is a major health problem in the US and many Western countries, with more than half of the population being overweight or obese. Yet, despite intense research efforts into the mechanisms underlying obesity and into the development of novel pharmacologic interventions, bariatric surgery, including gastric bypass surgery is the only successful treatment for severe obesity (le Roux, 2006; le Roux, 2007). Mimicking one of the effects of bariatric surgery, e.g. the increased secretion of glucagon-like peptide 1 (GLP-1) could be an effective strategy against obesity (Torekov, 2011).
The impact of gut peptides on the brain in the regulation of ingestive behavior is an area of great interest, since the involved signaling mechanisms may be potential targets for the treatment of obesity. Both endocrine, paracrine and neurocrine (vagal) signaling pathways are involved in gut to brain signaling of nutrient related information (Holst, 2007). Human studies have demonstrated that long acting hormones like leptin and insulin act on brain regions such as the hypothalamus and brainstem, influencing both food intake and response (Ahima, 2010). More short -term gut signals relayed by hormones such as CCK and PYY have also been shown in humans to have an effect on subcortical regions (including the hypothalamus, nucleus tractus solitarius (NTS), pons, thalamus) as well as on cortical regions (middle temporal gyrus, insula and anterior cingulate cortex (ACC) (Ahima, 2010). Whereas CCK infusion in healthy human subjects was found to result in increased activity primarily in homeostatic brain regions (hypothalamus, brainstem), PYY infusions were associated with increased activity in regions of reward-circuits (orbitalfrontal cortex, insula, anterior cingulate cortex). To our knowledge, the central effects of GLP-1 in humans have not been studied. (Ahima, 2010)
HYPOTHESIS
- Exenatide changes intrinsic activity in the NTS and hypothalamus, and connectivity between NTS and homeostatic and hedonic brain circuits
- These changes are seen both in lean and in obese subjects
- Changes in the engagement of brain circuits induced by Exenatide are correlated with increased ratings of satiety following a test meal
METHODS
The study design is a double-blind, placebo controlled, crossover study.
Twenty healthy female subjects between the ages of 18-40 years are needed The subjects will be divided into two age-matched groups of obese and lean women. The ten obese females will have a BMI between 30-35kg/ m2 and the 10 lean females will have a BMI between 19-25kg/m2. All subjects will be asked to participate in the entire protocol of 3 visits. There will be a screening visit to determine eligibility followed by two functional MRI visits where the subject is given a subcutaneous injection (sc) of 10ug of Exenatide (a GLP-1 analog) at one visit and a an injection of saline at the other MRI visit. The choice of female participants is based on the greater prevalence of obesity in women and the longstanding interest of the center's interest in women's health. In order to control for menstrual cycle hormonal fluctuation all participants will be scanned during the follicular phase of the menstrual cycle, for this study defined as the 4th-12th day after starting menstruation.
Screening (Visit 1):
All potential subjects will be asked to complete an initial screening visit approximately 1.5 hours of time. This visit will take place at the Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress at 10833 Le Conte Ave., Los Angeles, CA 90095 Room 47-126. At the beginning of this visit, the subject will be given ample time to read and sign the informed consent. The protocol will be discussed and reviewed with a study MD or RN.
The screening will include a medical history and physical examination. A urine test for pregnancy will also be done. If the pregnancy test is positive the subject will be immediately dropped from participation. Female subjects of child bearing potential will be asked to practice a medically approved birth control method during the study, including the oral contraceptive pill, abstinence, double barrier method (spermicide and condoms), or IUD. A menstrual cycle history will be obtained as part of the medical history and the first day of their last menses will be documented. fMRI visits will be planned during the follicular stage- specifically day 4-12 of their cycle. A 5 cc (1 tsp) blood draw for glucose will be collected. If the non- fasting blood glucose result is more than 200mg/dl the subject will be considered a screen fail. This value was chosen in order to exclude subjects with undiagnosed underlying diabetes.
Subjects will be asked to fill out several behavioral questionnaires: the UCLA bowel symptom questionnaire (BSQ 5.0), the Hospital Anxiety and Depression scale (HAD), the Spielberger State and Trait Anxiety Inventory (STAI-Y1 and Y2) and the MRI safety screening questionnaire; requiring about 20 minutes to complete.
The RN, NP or MD will review the inclusion and exclusion criteria with the subject to determine eligibility.
A brief structured psychological interview (MINI+) will be done to identify any major Axis I psychiatric disorders in DSM-IV and ICD-10, such as anxiety, depression, substance abuse or phobias.
If the subject is eligible and wishes to participate, they will be provided with instructions for the following study visit. As noted this visit will be scheduled during the follicular phase of the individual's menstrual cycle.
Visit 2 MRI scanning visit 1:
This visit will take approximately 2 hours of time. Subject will be asked to fast (except water) for eight hours prior to admission. Eligibility criteria for continuance in the study, including adverse events and any change in medication usage will be reviewed and recorded. The 1st day of last menstrual period will be noted and a urine pregnancy test will be performed. If positive the subject will be removed from study enrollment.
Subjects will be escorted to the CTSI (General clinical research area) and an IV will be placed for the four blood draws. A baseline fasting blood glucose will be done. It needs to be between 65mg/dl and 126mg/dl or the visit will be cancelled. The subject will then be escorted to the UCLA Ahmanson-Lovelace Brain Mapping Center, 660 Charles Young Dr. South, Los Angeles, CA 90095-7085 and prepared for scanning. Subjects will be asked to complete a PROMIS questionnaire prior to scanning to evaluate the previous nights sleep quality (for RSN analysis) and a Fullness Questionnaire (FQ); a visual analog scale used to measure hunger and satiety.
After wanding for metal safety they will be escorted into the MRI chamber. They will be given a synopsis of the study tests and prepared for placement in the scanner. They will be monitored for pulse oximetry and respiratory rate as a measure of autonomic nervous system and as a safety measure (after Exenatide injection) while scanning. These measures will be collected during all functional resting state network (RSN) scans.
Following placement structural scans will be done After the structural scans the subject will undergo a 10-minute resting state (RSN) scan during which then they will be asked to lie still with their eyes closed but not fall asleep.
After that RSN scan, subjects will be partially moved out of the scanner to receive either a subcutaneous injection of 10ug of Exenatide or a 0.5cc injection of saline (placebo) in the upper arm, thigh or abdomen. Randomization will be done by the UCLA research pharmacy where the drug is stored and dispensed. Subject and investigator will blinded to the randomization.
Immediately following the injection the subject will be moved back into the scanner and have a 8.5 minute structural scanner (MP Rage: a three-dimensional, T1-weighted, gradient-echo sequence used for study analysis). Immediately following the MP Rage, the subject will have the second 10-minute RSN scan (10-minutes post drug) with the same RSN instructions. After the second RSN scan is completed the subjects will complete the second Fullness Questionnaire (FQ). This will be presented on the screen via goggles and the answers will be given to the scanner operator via intercom. The subject will then be partially moved out of the scanner for a 1 teaspoon (5cc) blood draw. This serum sample will be for glucose, insulin and exenatide pharmacokinetic.
The subject will then be moved back into the scanner for the third and final 10-minute RSN with the same previous instructions. Immediately following this scan the subject will complete the third FQ and have 1 teaspoon (5cc) of blood drawn for glucose, insulin and Exenatide pharmacokinetic levels.
After scanning, subjects will be taken to the CTSI and provided a full balanced standard meal of 1200 calories. All subjects will have 2 lunch meal choices to choose from (chicken or ham) and will be instructed to "eat until you are full". After the meal, the subject will complete the fourth FQ and a final 5cc blood draw for glucose, insulin and Exenatide PK level. Approximate blood sampling for the whole day will be 1-2 ounces.
All scanning will be done in the morning, between ~9am-12pm, to account for hormonal fluctuation and for fasting comfort of the subject.
Visit 3 MRI scanning Visit 2:
Visit 3 is identical to Visit 2 except the subject will receive the opposite injection. If the subject was randomized to receive 10ug of Exenatide during Visit 2 then she will receive .5cc of saline (placebo) during Visit 3. Otherwise study procedures will be identical.
- Conditions
- Obesity
- Being tested
- Exenatide, Normal saline .2cc subcutaneous injection
- Keywords
- functional MRI, Structural MRI, obesity, resting state networks
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ExenatideDrug
Also called Byetta
10mcg sc (subcutaneous) injection once at one of the 2 MRI visits
Normal saline .2cc subcutaneous injectionDrug
sterile saline injection
| Study group | Role | What they receive |
|---|---|---|
| Exenatide | Active comparator | Exenatide injection 10 mcg subcutaneous Receives: Drug: Exenatide |
| Saline | Placebo comparator | .2cc SC injection of sterile normal saline Receives: Drug: Normal saline .2cc subcutaneous injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resting State networks in the brain
The proposed study aims to address two important questions regarding the mechanisms underlying the weight loss associated with exenatide. Our primary study objective is to determine whether Exenatide changes the resting state activity of the brain, and alters the connectivity between brain regions involved in homeostatic and hedonic brain circults.
Measured: one year
Secondary outcomes (1)
Age and body size differences
The secondary study objective is to determine if/how these changes differ between lean and obese subjects
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 posted29 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionDec 2012
- Study completionFeb 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- Amylin Pharmaceuticals, LLC.
- Responsible party
- Principal investigator, Lisa Kilpatrick, PhD, University of California, Los Angeles
- Investigators
- Emeran A Mayer, MD/co-PI, Study director, Oppenheimer Family Center for Neurobiology of Stress at UCLALisa Kilpatrick, PhD, Principal investigator, Oppenheimer Family Center for Neurobiology of Stress at UCLA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01501084
- Sponsor's protocol ID
- 11-002316
- Status last verified
- Nov 2017
- First submitted
- 20 Dec 2011
- Last updated
- 7 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of the GLP-1 Exenatide on Intrinsic Brain Activity in Lean and Obese Women
- ClinicalTrials.gov ID
- NCT01501084
- Acronym / sponsor ID
- 11-002316
- Conditions
- Obesity
- Keywords
- functional MRI, Structural MRI, obesity, resting state networks
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- Amylin Pharmaceuticals, LLC.
- Study start
- Dec 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Feb 2013 (actual)
- First posted
- 29 Dec 2011 (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.
Obesity is a major health problem in the US and many Western countries, with more than half of the population being overweight or obese. Yet, despite intense research efforts into the mechanisms underlying obesity and into the development of novel pharmacologic interventions, bariatric surgery, including gastric bypass surgery is the only successful treatment for severe obesity. Mimicking one of the effects of bariatric surgery, e.g. the increased secretion of glucagon-like peptide 1 (GLP-1) could be an effective strategy against obesity.
Obese individuals may be more sensitive to the rewarding aspects of food and less responsive to signals from the gut about actual energy needs. Using functional MRI scanning the investigators plan to examine the effect of Exenatide (a GLP-1 analog known to reduce caloric intake and produce weight loss in both obese and lean individuals) on activity within brain regions/networks involved in reward/motivation and in regulation of energy requirements. The investigators expect the peptide to change the balance between desire to eat for pleasure and the need to eat to maintain homeostasis.
Detailed description
PRIMARY STUDY OBJECTIVE The proposed study aims to address two important questions regarding the mechanisms underlying the weight loss associated with exenatide. The investigators primary study objective is to determine whether Exenatide changes the resting state activity of the brain, and alters the connectivity between brain regions involved in homeostatic and hedonic brain circuits.
SECONDARY STUDY OBJECTIVE The secondary study objective is to determine if/how these changes differ between lean and obese subjects
SIGNIFICANCE Obesity is a major health problem in the US and many Western countries, with more than half of the population being overweight or obese. Yet, despite intense research efforts into the mechanisms underlying obesity and into the development of novel pharmacologic interventions, bariatric surgery, including gastric bypass surgery is the only successful treatment for severe obesity (le Roux, 2006; le Roux, 2007). Mimicking one of the effects of bariatric surgery, e.g. the increased secretion of glucagon-like peptide 1 (GLP-1) could be an effective strategy against obesity (Torekov, 2011).
The impact of gut peptides on the brain in the regulation of ingestive behavior is an area of great interest, since the involved signaling mechanisms may be potential targets for the treatment of obesity. Both endocrine, paracrine and neurocrine (vagal) signaling pathways are involved in gut to brain signaling of nutrient related information (Holst, 2007). Human studies have demonstrated that long acting hormones like leptin and insulin act on brain regions such as the hypothalamus and brainstem, influencing both food intake and response (Ahima, 2010). More short -term gut signals relayed by hormones such as CCK and PYY have also been shown in humans to have an effect on subcortical regions (including the hypothalamus, nucleus tractus solitarius (NTS), pons, thalamus) as well as on cortical regions (middle temporal gyrus, insula and anterior cingulate cortex (ACC) (Ahima, 2010). Whereas CCK infusion in healthy human subjects was found to result in increased activity primarily in homeostatic brain regions (hypothalamus, brainstem), PYY infusions were associated with increased activity in regions of reward-circuits (orbitalfrontal cortex, insula, anterior cingulate cortex). To our knowledge, the central effects of GLP-1 in humans have not been studied. (Ahima, 2010)
HYPOTHESIS
- Exenatide changes intrinsic activity in the NTS and hypothalamus, and connectivity between NTS and homeostatic and hedonic brain circuits
- These changes are seen both in lean and in obese subjects
- Changes in the engagement of brain circuits induced by Exenatide are correlated with increased ratings of satiety following a test meal
METHODS
The study design is a double-blind, placebo controlled, crossover study.
Twenty healthy female subjects between the ages of 18-40 years are needed The subjects will be divided into two age-matched groups of obese and lean women. The ten obese females will have a BMI between 30-35kg/ m2 and the 10 lean females will have a BMI between 19-25kg/m2. All subjects will be asked to participate in the entire protocol of 3 visits. There will be a screening visit to determine eligibility followed by two functional MRI visits where the subject is given a subcutaneous injection (sc) of 10ug of Exenatide (a GLP-1 analog) at one visit and a an injection of saline at the other MRI visit. The choice of female participants is based on the greater prevalence of obesity in women and the longstanding interest of the center's interest in women's health. In order to control for menstrual cycle hormonal fluctuation all participants will be scanned during the follicular phase of the menstrual cycle, for this study defined as the 4th-12th day after starting menstruation.
Screening (Visit 1):
All potential subjects will be asked to complete an initial screening visit approximately 1.5 hours of time. This visit will take place at the Gail and Gerald Oppenheimer Family Center for Neurobiology of Stress at 10833 Le Conte Ave., Los Angeles, CA 90095 Room 47-126. At the beginning of this visit, the subject will be given ample time to read and sign the informed consent. The protocol will be discussed and reviewed with a study MD or RN.
The screening will include a medical history and physical examination. A urine test for pregnancy will also be done. If the pregnancy test is positive the subject will be immediately dropped from participation. Female subjects of child bearing potential will be asked to practice a medically approved birth control method during the study, including the oral contraceptive pill, abstinence, double barrier method (spermicide and condoms), or IUD. A menstrual cycle history will be obtained as part of the medical history and the first day of their last menses will be documented. fMRI visits will be planned during the follicular stage- specifically day 4-12 of their cycle. A 5 cc (1 tsp) blood draw for glucose will be collected. If the non- fasting blood glucose result is more than 200mg/dl the subject will be considered a screen fail. This value was chosen in order to exclude subjects with undiagnosed underlying diabetes.
Subjects will be asked to fill out several behavioral questionnaires: the UCLA bowel symptom questionnaire (BSQ 5.0), the Hospital Anxiety and Depression scale (HAD), the Spielberger State and Trait Anxiety Inventory (STAI-Y1 and Y2) and the MRI safety screening questionnaire; requiring about 20 minutes to complete.
The RN, NP or MD will review the inclusion and exclusion criteria with the subject to determine eligibility.
A brief structured psychological interview (MINI+) will be done to identify any major Axis I psychiatric disorders in DSM-IV and ICD-10, such as anxiety, depression, substance abuse or phobias.
If the subject is eligible and wishes to participate, they will be provided with instructions for the following study visit. As noted this visit will be scheduled during the follicular phase of the individual's menstrual cycle.
Visit 2 MRI scanning visit 1:
This visit will take approximately 2 hours of time. Subject will be asked to fast (except water) for eight hours prior to admission. Eligibility criteria for continuance in the study, including adverse events and any change in medication usage will be reviewed and recorded. The 1st day of last menstrual period will be noted and a urine pregnancy test will be performed. If positive the subject will be removed from study enrollment.
Subjects will be escorted to the CTSI (General clinical research area) and an IV will be placed for the four blood draws. A baseline fasting blood glucose will be done. It needs to be between 65mg/dl and 126mg/dl or the visit will be cancelled. The subject will then be escorted to the UCLA Ahmanson-Lovelace Brain Mapping Center, 660 Charles Young Dr. South, Los Angeles, CA 90095-7085 and prepared for scanning. Subjects will be asked to complete a PROMIS questionnaire prior to scanning to evaluate the previous nights sleep quality (for RSN analysis) and a Fullness Questionnaire (FQ); a visual analog scale used to measure hunger and satiety.
After wanding for metal safety they will be escorted into the MRI chamber. They will be given a synopsis of the study tests and prepared for placement in the scanner. They will be monitored for pulse oximetry and respiratory rate as a measure of autonomic nervous system and as a safety measure (after Exenatide injection) while scanning. These measures will be collected during all functional resting state network (RSN) scans.
Following placement structural scans will be done After the structural scans the subject will undergo a 10-minute resting state (RSN) scan during which then they will be asked to lie still with their eyes closed but not fall asleep.
After that RSN scan, subjects will be partially moved out of the scanner to receive either a subcutaneous injection of 10ug of Exenatide or a 0.5cc injection of saline (placebo) in the upper arm, thigh or abdomen. Randomization will be done by the UCLA research pharmacy where the drug is stored and dispensed. Subject and investigator will blinded to the randomization.
Immediately following the injection the subject will be moved back into the scanner and have a 8.5 minute structural scanner (MP Rage: a three-dimensional, T1-weighted, gradient-echo sequence used for study analysis). Immediately following the MP Rage, the subject will have the second 10-minute RSN scan (10-minutes post drug) with the same RSN instructions. After the second RSN scan is completed the subjects will complete the second Fullness Questionnaire (FQ). This will be presented on the screen via goggles and the answers will be given to the scanner operator via intercom. The subject will then be partially moved out of the scanner for a 1 teaspoon (5cc) blood draw. This serum sample will be for glucose, insulin and exenatide pharmacokinetic.
The subject will then be moved back into the scanner for the third and final 10-minute RSN with the same previous instructions. Immediately following this scan the subject will complete the third FQ and have 1 teaspoon (5cc) of blood drawn for glucose, insulin and Exenatide pharmacokinetic levels.
After scanning, subjects will be taken to the CTSI and provided a full balanced standard meal of 1200 calories. All subjects will have 2 lunch meal choices to choose from (chicken or ham) and will be instructed to "eat until you are full". After the meal, the subject will complete the fourth FQ and a final 5cc blood draw for glucose, insulin and Exenatide PK level. Approximate blood sampling for the whole day will be 1-2 ounces.
All scanning will be done in the morning, between ~9am-12pm, to account for hormonal fluctuation and for fasting comfort of the subject.
Visit 3 MRI scanning Visit 2:
Visit 3 is identical to Visit 2 except the subject will receive the opposite injection. If the subject was randomized to receive 10ug of Exenatide during Visit 2 then she will receive .5cc of saline (placebo) during Visit 3. Otherwise study procedures will be identical.
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 |
|---|---|---|
| Exenatide | Active comparator | Drug: ExenatideExenatide injection 10 mcg subcutaneous |
| Saline | Placebo comparator | Drug: Normal saline .2cc subcutaneous injection.2cc SC injection of sterile normal saline |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- FEMALES 18 to 40 years of age, inclusive
- Lean control subjects with BMI's between 19 and 25kg/m2.
- Obese subjects with BMI's between 30 and 35kg/m2.
- Willingness to participate in this study as evidenced by a signed, written informed consent form (ICF).
- Willingness to avoid pregnancy and practice adequate birth control (abstinence, oral contraception, intrauterine devices, implantable devices, or barrier method with spermicide) during the time of study enrollment.
Key exclusion criteria (20 listed)
- Evidence of structural abnormality of the gastrointestinal tract or GI diseases/conditions. Exclusionary GI conditions include but are not limited to: gastrointestinal surgery (exceptions: appendectomy, benign polypectomy, cholecystectomy), pancreatitis, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), esophagitis (exception: symptom controlled reflux disease), celiac disease, gastrointestinal malignancy or obstruction, functional dyspepsia, peptic ulcer disease, lactose intolerance or any malabsorptive condition.
- Clinical evidence of cardiovascular, respiratory, renal, hepatic, malignancy, hematologic, neurologic (including regular migraines defined as more than 1 migraine per month), psychiatric or any disease that the PI determines may interfere with safe participation in the study.
- Subjects with current psychiatric disorder, or history of such disorder in the past 5 years. This list includes but is not limited to bipolar disorder, alcohol or substance abuse/dependence, suicide attempt or behavior, or presence of anxiety or depression at the time of screening. Poorly controlled anxiety or depression will be determined as a result of MINI + interview by the clinician at screening.
- Current history of chronic pain.
- Use of investigational drugs, products or devices within 28 days prior to screen and through study participation.
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 |
|---|---|---|
| ExenatideAlso: Byetta10mcg sc (subcutaneous) injection once at one of the 2 MRI visits | Drug | Exenatide |
| Normal saline .2cc subcutaneous injectionsterile saline injection | Drug | Saline |
Primary outcome
Resting State networks in the brain
Time frame: one year
The proposed study aims to address two important questions regarding the mechanisms underlying the weight loss associated with exenatide. Our primary study objective is to determine whether Exenatide changes the resting state activity of the brain, and alters the connectivity between brain regions involved in homeostatic and hedonic brain circults.
1 secondary outcome
Age and body size differences
Time frame: one year
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 7 Nov 2017.
- Individual participant dataSharing planned: Yes
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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.
Emeran A Mayer, MD/co-PI study director
Oppenheimer Family Center for Neurobiology of Stress at UCLA
Lisa Kilpatrick, PhD principal investigator
Oppenheimer Family Center for Neurobiology of Stress at UCLA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Exenatide and Normal saline .2cc subcutaneous injection in people with Obesity, run by University of California, Los Angeles 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 12 inclusion and 20 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 7 Nov 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Resting State networks in the brain (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 7 Nov 2017.