ObesityPhase 2NCT01083108

Effects of Caloric Restriction Alone Versus Postoperative Caloric Restriction Following Bariatric Surgery on Glucose Metabolism in Patients With Diabetes Mellitus

A Phase 2 study testing Roux-en-Y Gastric Bypass and Caloric Restriction in people with Obesity and Bariatric Surgery, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Background: Bariatric surgery is the most effective way to achieve significant, long-term weight loss. It has also been shown to be an effective therapy for obese individuals with type 2 diabetes: more than 70 percent of patients no longer need medications for diabetes after surgery. Read more about this study

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Obesity, Bariatric Surgery, Morbid Obesity
What is being tested?: Roux-en-Y Gastric Bypass and Caloric Restriction
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 3 sitesUnited States
Study dates: 31 Mar 2011to 13 Dec 2019
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 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Clinical diagnosis of Type 2 diabetes mellitus
Age 18-60 years
Body mass index greater than or equal to 35 kg/m(2)
Either
--a. Patients scheduled for Roux-en-Y gastric bypass at Vanderbilt University Medical Center or University of Maryland
OR
--b. Patients matched for race, sex, BMI (plus or minus 15%), and age (plus or minus 5 years) to RYGBP patients, above, but NOT scheduled for bariatric surgery.
Subjects must have an endocrinologist or primary care provider who manages their diabetes.

Who cannot join

Current use of insulin
Use of exenatide, sitagliptin (or other dipeptidyl peptidase inhibitor), thiazolidinediones, or experimental diabetes medication within the past 3 months
Medical condition that alters glucose metabolism (other than type 2 diabetes) or weight (e.g. chronic inflammatory diseases, monogenic obesity, Prader-Willi syndrome)
Current use of medication that alters glucose metabolism (other than oral diabetes medications) or weight (e.g. corticosteroids, atypical antipsychotic drugs)
Significant comorbidity that, in the opinion of the investigators, will increase risk to the subject, (e.g. current treatment for cancer, renal failure)
Positive urine pregnancy test or plans to become pregnant during the clinical trial

Show all 9Show fewer

Psychiatric or cognitive disorder that will, in the opinion of the investigators, limit the subject's ability to comply with study procedures
Body weight greater than 450 lbs
History of previous bariatric surgical procedure or other surgery altering the length or arrangement of the intestines (e.g. Whipple procedure)

Trial locations and contacts

3 sites in 1 country.

United States3 sites

University of Maryland, Baltimore
Baltimore, Maryland, 21201-1595
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
Vanderbilt University
Nashville, Tennessee, 37232

Other trials in United States

About this study

Background:

Bariatric surgery is the most effective way to achieve significant, long-term weight loss. It has also been shown to be an effective therapy for obese individuals with type 2 diabetes: more than 70 percent of patients no longer need medications for diabetes after surgery. This resolution of diabetes is predominately caused by marked weight loss resulting in improved insulin sensitivity. However, the beneficial effects of bariatric surgery on type 2 diabetes cannot be accounted for entirely by weight loss, because many bariatric surgery patients have resolution of diabetes within 1 week following bariatric surgery, even before they lose a clinically significant amount of weight.
One possible reason for the rapid resolution of diabetes after bariatric surgery .is that during the first week after surgery, patients can eat very little (about 300 Calories per day). It is well known that reducing calories to this level improves diabetes. Another possibility is that changes in the flow of food through the intestines may improve diabetes. Evidence for this comes from the observation that patients after gastric bypass have better glucose levels than those who have gastric banding. Researchers are interested in determining how much of the improvement in diabetes in the first week after Roux-en-Y gastric bypass (RYGBP) surgery is due to restricting calories, and how much is due to other factors, such as bypassing the upper part of the small intestine.

Objectives:

To determine the change in total body insulin sensitivity after RYGBP compared to caloric restriction without surgery.
To study possible reasons for improvements in diabetes after RYGBP.

Eligibility:

Individuals 18 to 60 years of age who have a body mass index (BMI) greater than 35 and have type 2 diabetes.

Design:

This is not a randomized study, and patients will not receive bariatric surgery as part of this study.

Two groups of patients will be studied: those scheduled for RYGBP surgery and those not undergoing surgery.

RYGBP Surgery Participants:
Up to 3 weeks before surgery, participants will spend 2 nights and days at the Vanderbilt University Clinical Research Center or the NIH Clinical Center for testing to learn about how their bodies handle sugar and use energy. During the 5 days prior to these tests, participants will be asked to not take diabetes medications, and will check blood sugar at least twice a day.
From 8 days before surgery, participants will begin an 800 Calorie per day liquid diet to prepare for surgery.
After surgery and discharge, participants will be readmitted to the Clinical Research Center at Vanderbilt or NIH for further tests and diet monitoring. Diabetes medications may be adjusted or stopped altogether based on the results of the tests.
Non-surgery Participants:
Participants will spend 2 nights and days in the NIH Clinical Center for testing to learn about how their bodies handle sugar and use energy. During the 5 days prior to these tests, participants will be asked to not take diabetes medications, and will check blood sugar at least twice a day.
After the tests, participants will begin an 800 Calorie per day liquid diet for 8 days.
After 8 days, participants will be readmitted to the Clinical Center at NIH for 1 week of further tests and a 300 Calorie per day diet. Diabetes medications may be adjusted or stopped altogether based on the results of the tests.

Read the detailed description

Background

Presently it is unknown whether the rapid normalization of glucose metabolism in obese patients with type 2 diabetes after bariatric surgery (before major weight loss occurs) is primarily due to acute postoperative caloric restriction or due to changes in intestinal effects on insulin secretion and sensitivity. We speculate that bypassing the stomach and proximal small intestine affects glucose metabolism beyond simple caloric restriction, and that the mechanisms are related to changes in hepatic and muscle insulin sensitivity, changes in vagal afferent signals, and changes in incretins and other gut hormones.

Aim

To compare the effects of pure caloric restriction with caloric restriction early after bariatric surgery (Roux-en-Y Gastric Bypass, RYGBP) in patients with type 2 diabetes, and to investigate the mechanisms that explain the observed difference in glucose metabolism

Methods

In patients with type 2 diabetes we will study the short-term changes in glucose metabolism, insulin sensitivity and gut hormone levels using a parallel group design. The non-surgical group will be studied before and after receiving a hypocaloric diet for 6 days mimicking the typical postoperative diet. The surgical group will be studied before and 6 days after bariatric surgery. The primary outcome will be the change in total body insulin sensitivity attributable to caloric restriction alone versus caloric restriction after RYGBP. Non-surgical subjects studied at NIH may enter an optional long-term weight loss phase.

Conditions: Obesity, Bariatric Surgery, Morbid Obesity, Diabetes Mellitus Type 2, Diet Therapy
Being tested: Roux-en-Y Gastric Bypass, Caloric Restriction
Keywords: Behavioral Weight Loss Treatment, Bariatric Surgery, Diabetes Type II, Obesity, Adult, Type 2 Diabetes
Medical subject headings: Obesity, Obesity, Morbid, Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Roux-en-Y Gastric BypassOther
The surgical group will be studied before and 6 days after bariatric surgery.
Caloric RestrictionOther
The non-surgical group will be studied before and after receiving a hypocaloric diet for 6 days mimicking the typical postoperative diet.

Study groups in NCT01083108
Study group	Role	What they receive
Non-surgical Arm	Active comparator	Low-calorie Diet Receives: Other: Caloric Restriction
Surgical Arm	Experimental	Roux-en-Y Gastric Bypass Receives: Other: Roux-en-Y Gastric Bypass

What is being measured

The primary outcome is the main question the study is designed to answer.

The primary outcome of the study is the change in total body insulin sensitivity due to RYGBP alone using the euglycemic hyperinsulinemic clamp technique.
Insulin sensitivity will be determined using the gold standard euglycemic hyperinsulinemic clamp method, which directly measures total body insulin sensitivity as the glucose disposal rate, M, during steady state conditions of euglycemia and hyperinsulinemia. A two- stage clamp will be performed, using first a low-dose insulin infusion (to determine hepatic insulin sensitivity), followed by a high-dose insulin infusion (to determine muscle insulin sensitivity).
Measured: 2 years

Secondary outcomes (1)

The secondary outcomes are changes in insulin sensitivity, insulin secretion, and gut hormones due to caloric restriction alone, caloric restriction plus RYGBP, and RYGBP alone.
In addition to assessing total body insulin sensitivity, we will evaluate hepatic insulin sensitivity, insulin secretion and gut hormones for threeconditions:1. Diet alone (Before vs. after 6 day caloric restriction in the non-surgical group)2. Diet plus bariatric surgery (Before vs. after 6 day caloric restriction and surgery in the RYGBP group)3. Bariatric surgery alone (After 6 day caloric restriction in RYGBP group vs. non-surgical group)
Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Mar 201113 Dec 2019

First posted9 Mar 2010 (estimated)
Study start31 Mar 2011
Primary completion22 May 2013
Study completion13 Dec 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (3)Papers the sponsor has linked to this study.
Other trials for ObesityStudies of the same condition, open and under way.
More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The 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: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01083108
Sponsor's protocol ID: 100064
Other IDs: 10-DK-0064
Status last verified: 13 Dec 2019
First submitted: 6 Mar 2010
Last updated: 17 Dec 2019
Results posted: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan;52(1):102-10. doi: 10.2337/diabetes.52.1.102.
PubMed 12502499
Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC. Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration? Diabetologia. 2005 Nov;48(11):2221-8. doi: 10.1007/s00125-005-1949-2. Epub 2005 Oct 5.
PubMed 16205882
Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999 Jun 2;281(21):2005-12. doi: 10.1001/jama.281.21.2005.
PubMed 10359389

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Caloric Restriction Alone Versus Postoperative Caloric Restriction Following Bariatric Surgery on Glucose Metabolism in Patients With Diabetes Mellitus
ClinicalTrials.gov ID: NCT01083108
Acronym / sponsor ID: 100064
Conditions: Obesity, Bariatric Surgery, Morbid Obesity, Diabetes Mellitus Type 2, Diet Therapy
Keywords: Behavioral Weight Loss Treatment, Bariatric Surgery, Diabetes Type II, Obesity, Adult, Type 2 Diabetes
Phase: Phase 2
Study type: Interventional
Recruitment status: Terminated
Enrolment: 5 participants (actual)
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
Study start: 31 Mar 2011
Primary completion: 22 May 2013 (actual)
Study completion: 13 Dec 2019 (actual)
First posted: 9 Mar 2010 (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.

Background:

Bariatric surgery is the most effective way to achieve significant, long-term weight loss. It has also been shown to be an effective therapy for obese individuals with type 2 diabetes: more than 70 percent of patients no longer need medications for diabetes after surgery. This resolution of diabetes is predominately caused by marked weight loss resulting in improved insulin sensitivity. However, the beneficial effects of bariatric surgery on type 2 diabetes cannot be accounted for entirely by weight loss, because many bariatric surgery patients have resolution of diabetes within 1 week following bariatric surgery, even before they lose a clinically significant amount of weight.
One possible reason for the rapid resolution of diabetes after bariatric surgery .is that during the first week after surgery, patients can eat very little (about 300 Calories per day). It is well known that reducing calories to this level improves diabetes. Another possibility is that changes in the flow of food through the intestines may improve diabetes. Evidence for this comes from the observation that patients after gastric bypass have better glucose levels than those who have gastric banding. Researchers are interested in determining how much of the improvement in diabetes in the first week after Roux-en-Y gastric bypass (RYGBP) surgery is due to restricting calories, and how much is due to other factors, such as bypassing the upper part of the small intestine.

Objectives:

To determine the change in total body insulin sensitivity after RYGBP compared to caloric restriction without surgery.
To study possible reasons for improvements in diabetes after RYGBP.

Eligibility:

Individuals 18 to 60 years of age who have a body mass index (BMI) greater than 35 and have type 2 diabetes.

Design:

This is not a randomized study, and patients will not receive bariatric surgery as part of this study.

Two groups of patients will be studied: those scheduled for RYGBP surgery and those not undergoing surgery.

RYGBP Surgery Participants:
Up to 3 weeks before surgery, participants will spend 2 nights and days at the Vanderbilt University Clinical Research Center or the NIH Clinical Center for testing to learn about how their bodies handle sugar and use energy. During the 5 days prior to these tests, participants will be asked to not take diabetes medications, and will check blood sugar at least twice a day.
From 8 days before surgery, participants will begin an 800 Calorie per day liquid diet to prepare for surgery.
After surgery and discharge, participants will be readmitted to the Clinical Research Center at Vanderbilt or NIH for further tests and diet monitoring. Diabetes medications may be adjusted or stopped altogether based on the results of the tests.
Non-surgery Participants:
Participants will spend 2 nights and days in the NIH Clinical Center for testing to learn about how their bodies handle sugar and use energy. During the 5 days prior to these tests, participants will be asked to not take diabetes medications, and will check blood sugar at least twice a day.
After the tests, participants will begin an 800 Calorie per day liquid diet for 8 days.
After 8 days, participants will be readmitted to the Clinical Center at NIH for 1 week of further tests and a 300 Calorie per day diet. Diabetes medications may be adjusted or stopped altogether based on the results of the tests.

Detailed description

Background

Aim

Methods

Study design

Primary purpose: Other
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Non-surgical Arm	Active comparator	Other: Caloric RestrictionLow-calorie Diet
Surgical Arm	Experimental	Other: Roux-en-Y Gastric BypassRoux-en-Y Gastric Bypass

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (8 listed)

--a. Patients scheduled for Roux-en-Y gastric bypass at Vanderbilt University Medical Center or University of Maryland
OR
--b. Patients matched for race, sex, BMI (plus or minus 15%), and age (plus or minus 5 years) to RYGBP patients, above, but NOT scheduled for bariatric surgery.

Key exclusion criteria (9 listed)

Current use of insulin
Use of exenatide, sitagliptin (or other dipeptidyl peptidase inhibitor), thiazolidinediones, or experimental diabetes medication within the past 3 months
Medical condition that alters glucose metabolism (other than type 2 diabetes) or weight (e.g. chronic inflammatory diseases, monogenic obesity, Prader-Willi syndrome)
Current use of medication that alters glucose metabolism (other than oral diabetes medications) or weight (e.g. corticosteroids, atypical antipsychotic drugs)
Significant comorbidity that, in the opinion of the investigators, will increase risk to the subject, (e.g. current treatment for cancer, renal failure)

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
Roux-en-Y Gastric BypassThe surgical group will be studied before and 6 days after bariatric surgery.	Other	Surgical Arm
Caloric RestrictionThe non-surgical group will be studied before and after receiving a hypocaloric diet for 6 days mimicking the typical postoperative diet.	Other	Non-surgical Arm

Primary outcome

The primary outcome of the study is the change in total body insulin sensitivity due to RYGBP alone using the euglycemic hyperinsulinemic clamp technique.
Time frame: 2 years
Insulin sensitivity will be determined using the gold standard euglycemic hyperinsulinemic clamp method, which directly measures total body insulin sensitivity as the glucose disposal rate, M, during steady state conditions of euglycemia and hyperinsulinemia. A two- stage clamp will be performed, using first a low-dose insulin infusion (to determine hepatic insulin sensitivity), followed by a high-dose insulin infusion (to determine muscle insulin sensitivity).

1 secondary outcome

The secondary outcomes are changes in insulin sensitivity, insulin secretion, and gut hormones due to caloric restriction alone, caloric restriction plus RYGBP, and RYGBP alone.
Time frame: 2 years

Results and safety

The study was stopped early. Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
Background: PubMed 12502499Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan;52(1):102-10. doi: 10.2337/diabetes.52.1.102.
Background: PubMed 16205882Meier JJ, Bhushan A, Butler AE, Rizza RA, Butler PC. Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration? Diabetologia. 2005 Nov;48(11):2221-8. doi: 10.1007/s00125-005-1949-2. Epub 2005 Oct 5.
Background: PubMed 10359389Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999 Jun 2;281(21):2005-12. doi: 10.1001/jama.281.21.2005.

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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.

Kristina I Rother, M.D. principal investigator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 9 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: stopped early, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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. 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 stopped early. Results are not available in the source record.

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?

The primary outcome of the study is the change in total body insulin sensitivity due to RYGBP alone using the euglycemic hyperinsulinemic clamp technique. (time frame: 2 years). 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 NCT01083108, which also lists 3 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 17 Dec 2019.