ObesityPhase 2NCT02697253
Mechanisms Underlying Predictors of Success From Obesity Surgery
A Phase 2 study testing Exendin 9-39 and Sitagliptin in people with Obesity, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
The goal of this project is to identify predictors of success in the treatment of obesity after bariatric surgery. The specific aims of this proposal are to: 1. Employ behavioral tests of mechanisms that control food intake in normal weight individuals, to determine which intake control mechanisms lead to changes… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Obesity
- What is being tested?
- Exendin 9-39 and Sitagliptin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to 29 Jul 2021
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- BMI >35 kg/m2 BMI
- BMI < 65 kg/m2
- Preparing to undergo Roux-en-Y gastric bypass or gastric sleeve (RYGB/GS) surgery at St. Luke-Roosevelt Hospital
- Within the 18-65 age range
- Blood pressure under <160/100 mmHg
- Fasting triglyceride <600 mg/dl
- No recent (last 6 months) history of cardiovascular disease.
- Prior history of angioplasty or coronary artery bypass surgery with a normal stress test will not be a contraindication.
Who cannot join
- Diabetes Mellitus
- Active cancer
- Unstable angina
- Recent stroke
- Current therapy that may affect glucose metabolism such as glucocorticoids, adrenergic agents
- Active infection
Show all 20Show fewer
- Kidney failure
- Severe liver dysfunction
- Heavy alcohol use
- Severe respiratory or cardiac failure
- Pancreatitis
- History of bullous pemphigoid
- Pregnancy
- Patients who are currently or have had prior GLP-1 therapy.
- Patients with known hypersensitivity to Exendin 9-39 or similar products, albumin, sitagliptin and/or acetaminophen will also be excluded.
- Additional exclusions for visits 4 and 5 ONLY:
- Patients at risk for heart disease, such as patients with a history of atherosclerotic cardiovascular disease and history of heart failure
- Renal impairment (eGFR˂60 Ml/MIN/1.73 M2)
- History of exfoliative skin conditions in particularly if occurring with a DPP-4 inhibitor use
- History of bullous pemphigoid and Stevens-Johnson syndrome.
Trial locations and contacts
1 site in 1 country.
About this study
The goal of this project is to identify predictors of success in the treatment of obesity after bariatric surgery. The specific aims of this proposal are to:
- Employ behavioral tests of mechanisms that control food intake in normal weight individuals, to determine which intake control mechanisms lead to changes after Roux-en-y gastric bypass (RYGB) or sleeve gastrectomy (SG); and
- Measure behavioral and psycho-social predictors of weight loss and food intake reduction, so as to determine which are most predictive of successful weight loss and food intake reduction.
- Account for success in reduction of food intake brought about by the pattern of hormone release, particularly glucagon-like peptide-1 (GLP-1), Peptide YY (PYY) and gastric distention, known to underlie satiation, coupled with post-ingestive changes in reinforcing value of food and motivation to consume.
Tests of the hypothesis will be done by measuring responses to tasting, working for, and consuming, foods on sensory, motivational, cognitive, and physiological variables, including amount consumed and rate of eating under standardized conditions, before surgery and at a two year follow up visit. In addition, the inhibitor sitagliptin will be administered the night before and day of test meal and exendin-9-39 (EX9) will be infused before and during the meal to determine whether blockade of GLP-1 / PYY receptors after surgery reverses intake reduction. Investigators predict that successful patients will show changes that favor reduction in food intake, rate of eating, motivation to consume, reward value of foods, and a hormone profile that has been shown to generate satiation and maintain reduction in intake (e.g. increased Cholecystokinin (CCK), GLP-1, PYY, reduced ghrelin). To the extent that psycho-social and cognitive factors may override physiological brakes to eating behavior, the subjects may fail to achieve success, and consequently the failure may be predicted from over-impulsiveness or inability to suppress working for rewarding food stimuli. To test these hypotheses, a total of 83 patients will be enrolled prior to RYGB/SG and restudied 2 years after the surgery. The sitagliptin / EX9 studies will be done in a subset of 32 completers. To test this aim, patients will be divided into 4 groups of 19. The 4 patients from each group with the most weight loss (% weight loss ≥35 at 2 years post-surgery, 16 patients in total) and least weight loss (% weight loss of ≤25 at two years 16 patients in total) will be recruited for these two additional post-operative visits within one year of completing Visit #3 after the RYGB/SG surgery. A total of 32 patients will be recruited for visits 4 and 5.
Read the detailed description
Obesity is a major public health as well as economic (expense of treating) problem world-wide, and Roux-en-Y gastric bypass (RYGB) and Sleeve Gastrectomy (SG) surgeries are effective treatments. A barrier to progress is that between 25% and 40% patients were not successful in achieving and maintaining at least 30% weight loss, which is considered medically successful for this operation. Understanding the mechanisms that contribute to success or failure of this operation is an unsolved problem in obesity research, which this proposal is addressing. The focus of this project is to identify mechanisms that contribute to suppression of food intake following bariatric surgery, and to investigate whether these mechanisms predict long-term success following bariatric surgery
- Conditions
- Obesity
- Being tested
- Exendin 9-39 and Sitagliptin, Placebo
- Keywords
- Roux-en-Y Bariatric Surgery, Psychosocial Variables, Behavioral Variables, Weight Loss, Food Intake, GLP-1, Reinforcing Value of Food, Exendin 9-39
- Medical subject headings
- Obesity, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exendin 9-39 and SitagliptinDrug
Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.
100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours.
PlaceboDrug
Infusion of 0.9% saline solution (placebo infusion) for 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.
100mg Placebo tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg placebo tablet at 0700 hours.
| Study group | Role | What they receive |
|---|---|---|
| Successful drug | Experimental | Participants who have a % weight loss ≥35 at 2 years post RYGB/SG surgery will be administered sitagliptin and receive infusion of Exendin 9-39 prior to an intake test.
Drug: Exendin 9-39 Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.
Drug: Sitagliptin 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours. Receives: Drug: Exendin 9-39 and Sitagliptin |
| Unsuccessful drug | Experimental | Participants who have a % weight loss of ≤25 at two years post RYGB/SG surgery will be administered Sitagliptin and receive infusion of Exendin 9-39 prior to an intake test.
Drug: Exendin 9-39 Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.
Drug: Sitagliptin 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours. Receives: Drug: Exendin 9-39 and Sitagliptin |
| Success placebo | Placebo comparator | Participants who have a % weight loss ≥35 at 2 years post RYGB/SG surgery will be administered a placebo and receive a placebo infusion prior to an intake test.
Drug: Placebo Infusion of 0.9% saline solution (placebo infusion) for 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.
Drug: Placebo 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours. Receives: Drug: Placebo |
| Unsuccess placebo | Placebo comparator | Participants who have a % weight loss of ≤25 at two years post RYGB/SG surgery will be administered a placebo and receive a placebo infusion prior to an intake test.
Drug: Placebo Infusion of 0.9% saline solution (placebo infusion) for 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload.
Drug: Placebo 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Successful Weight Loss
% Excess body weight lost
Measured: 2 years
Secondary outcomes (3)
Intake amount in grams consumed in a food intake capacity test
Intake amount in grams consumed in a food intake capacity test
Measured: 2 years
Fullness levels based on a rating scale after food intake capacity test
Fullness levels based on a rating scale after food intake capacity test
Measured: 2 years
Sickness levels based on a rating scale after food intake capacity test
Sickness levels based on a rating scale after food intake capacity test
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2016 (estimated)
- Study startJan 2016
- Primary completion29 Jul 2021
- Study completion29 Jul 2021
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 Icahn School of Medicine at Mount SinaiThe 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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Harry Kissileff, Icahn School of Medicine at Mount Sinai
- Investigators
- Harry Kissileff, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02697253
- Sponsor's protocol ID
- GCO 15-1990
- Other IDs
- R01DK108643, AAAQ1904
- Status last verified
- Nov 2022
- First submitted
- 23 Feb 2016
- Last updated
- 15 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms Underlying Predictors of Success From Obesity Surgery
- ClinicalTrials.gov ID
- NCT02697253
- Acronym / sponsor ID
- GCO 15-1990
- Conditions
- Obesity
- Keywords
- Roux-en-Y Bariatric Surgery, Psychosocial Variables, Behavioral Variables, Weight Loss, Food Intake, GLP-1, Reinforcing Value of Food, Exendin 9-39
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Jan 2016
- Primary completion
- 29 Jul 2021 (actual)
- Study completion
- 29 Jul 2021 (actual)
- First posted
- 3 Mar 2016 (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.
The goal of this project is to identify predictors of success in the treatment of obesity after bariatric surgery. The specific aims of this proposal are to:
- Employ behavioral tests of mechanisms that control food intake in normal weight individuals, to determine which intake control mechanisms lead to changes after Roux-en-y gastric bypass (RYGB) or sleeve gastrectomy (SG); and
- Measure behavioral and psycho-social predictors of weight loss and food intake reduction, so as to determine which are most predictive of successful weight loss and food intake reduction.
- Account for success in reduction of food intake brought about by the pattern of hormone release, particularly glucagon-like peptide-1 (GLP-1), Peptide YY (PYY) and gastric distention, known to underlie satiation, coupled with post-ingestive changes in reinforcing value of food and motivation to consume.
Tests of the hypothesis will be done by measuring responses to tasting, working for, and consuming, foods on sensory, motivational, cognitive, and physiological variables, including amount consumed and rate of eating under standardized conditions, before surgery and at a two year follow up visit. In addition, the inhibitor sitagliptin will be administered the night before and day of test meal and exendin-9-39 (EX9) will be infused before and during the meal to determine whether blockade of GLP-1 / PYY receptors after surgery reverses intake reduction. Investigators predict that successful patients will show changes that favor reduction in food intake, rate of eating, motivation to consume, reward value of foods, and a hormone profile that has been shown to generate satiation and maintain reduction in intake (e.g. increased Cholecystokinin (CCK), GLP-1, PYY, reduced ghrelin). To the extent that psycho-social and cognitive factors may override physiological brakes to eating behavior, the subjects may fail to achieve success, and consequently the failure may be predicted from over-impulsiveness or inability to suppress working for rewarding food stimuli. To test these hypotheses, a total of 83 patients will be enrolled prior to RYGB/SG and restudied 2 years after the surgery. The sitagliptin / EX9 studies will be done in a subset of 32 completers. To test this aim, patients will be divided into 4 groups of 19. The 4 patients from each group with the most weight loss (% weight loss ≥35 at 2 years post-surgery, 16 patients in total) and least weight loss (% weight loss of ≤25 at two years 16 patients in total) will be recruited for these two additional post-operative visits within one year of completing Visit #3 after the RYGB/SG surgery. A total of 32 patients will be recruited for visits 4 and 5.
Detailed description
Obesity is a major public health as well as economic (expense of treating) problem world-wide, and Roux-en-Y gastric bypass (RYGB) and Sleeve Gastrectomy (SG) surgeries are effective treatments. A barrier to progress is that between 25% and 40% patients were not successful in achieving and maintaining at least 30% weight loss, which is considered medically successful for this operation. Understanding the mechanisms that contribute to success or failure of this operation is an unsolved problem in obesity research, which this proposal is addressing. The focus of this project is to identify mechanisms that contribute to suppression of food intake following bariatric surgery, and to investigate whether these mechanisms predict long-term success following bariatric surgery
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Successful drug | Experimental | Drug: Exendin 9-39 and SitagliptinParticipants who have a % weight loss ≥35 at 2 years post RYGB/SG surgery will be administered sitagliptin and receive infusion of Exendin 9-39 prior to an intake test. Drug: Exendin 9-39 Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload. Drug: Sitagliptin 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours. |
| Unsuccessful drug | Experimental | Drug: Exendin 9-39 and SitagliptinParticipants who have a % weight loss of ≤25 at two years post RYGB/SG surgery will be administered Sitagliptin and receive infusion of Exendin 9-39 prior to an intake test. Drug: Exendin 9-39 Infusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload. Drug: Sitagliptin 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours. |
| Success placebo | Placebo comparator | Drug: PlaceboParticipants who have a % weight loss ≥35 at 2 years post RYGB/SG surgery will be administered a placebo and receive a placebo infusion prior to an intake test. Drug: Placebo Infusion of 0.9% saline solution (placebo infusion) for 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload. Drug: Placebo 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours. |
| Unsuccess placebo | Placebo comparator | Drug: PlaceboParticipants who have a % weight loss of ≤25 at two years post RYGB/SG surgery will be administered a placebo and receive a placebo infusion prior to an intake test. Drug: Placebo Infusion of 0.9% saline solution (placebo infusion) for 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload. Drug: Placebo 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- BMI >35 kg/m2 BMI
- BMI < 65 kg/m2
- Preparing to undergo Roux-en-Y gastric bypass or gastric sleeve (RYGB/GS) surgery at St. Luke-Roosevelt Hospital
- Within the 18-65 age range
- Blood pressure under <160/100 mmHg
Key exclusion criteria (20 listed)
- Diabetes Mellitus
- Active cancer
- Unstable angina
- Recent stroke
- Current therapy that may affect glucose metabolism such as glucocorticoids, adrenergic agents
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 |
|---|---|---|
| Exendin 9-39 and SitagliptinInfusion of exendin 9-39 at the rate of 600 pmol/kg/min, infusion time 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload. 100mg tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg tablet at 0700 hours. | Drug | Successful drug, Unsuccessful drug |
| PlaceboInfusion of 0.9% saline solution (placebo infusion) for 80 minutes. An average of 18.2mg will be infused in a forearm vein during an oral glucose (30g) preload. 100mg Placebo tablet will be administered at 2200 hours the night before the visit. The day of the visit, the patient will take another 100mg placebo tablet at 0700 hours. | Drug | Success placebo, Unsuccess placebo |
Primary outcome
Successful Weight Loss
Time frame: 2 years
% Excess body weight lost
3 secondary outcomes
Intake amount in grams consumed in a food intake capacity test
Time frame: 2 years
Fullness levels based on a rating scale after food intake capacity test
Time frame: 2 years
Sickness levels based on a rating scale after food intake capacity test
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2022.
- Individual participant dataSharing planned: No
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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.
Harry Kissileff, PhD principal investigator
Icahn School of Medicine at Mount Sinai
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 Exendin 9-39 and Sitagliptin in people with Obesity, run by Icahn School of Medicine at Mount Sinai 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 8 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: withdrawn, as of the sponsor's last update on 15 Nov 2022. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Successful Weight Loss (time frame: 2 years). 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 15 Nov 2022.