Diabetes MellitusNCT04263168
Glycemic Index Variations In the Early Period Following Bariatric Surgery
A study testing Continuous Glucose monitoring in the perioperative period in people with Diabetes Mellitus and Bariatric Surgery Candidate, run by Sheba Medical Center at 1 site in Israel.
Trial summary
The diverse community of gut microbes commonly referred to as the 'gut microbiome', is increasingly suggested to play significant roles in health and disease, and to affect even distant non-GI organs by metabolite signaling. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Diabetes Mellitus, Bariatric Surgery Candidate
- What is being tested?
- Continuous Glucose monitoring in the perioperative period
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Mar 2020to 1 Aug 2022
- Phase
- Interventional
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult Population (> 18 years old)
- Diabetic Patients (Type 2)
- Bariatric surgery candidates for two types of bariatric surgery, i.e. sleeve gastrectomy and Roux-en-Y gastric bypass
- Laparoscopic Cholecystectomy candidates
Who cannot join
- Pregnant Women
- < 18 years old
Trial locations and contacts
1 site in 1 country.
About this study
The diverse community of gut microbes commonly referred to as the 'gut microbiome', is increasingly suggested to play significant roles in health and disease, and to affect even distant non-GI organs by metabolite signaling. Type 2 diabetes mellitus (T2DM) patients feature a distinct gut microbiome signature4, while modulating the gut microbiome by either antibiotics or fecal microbial transplantation (FMT) is suggested to impact insulin sensitivity. Originally designed to treat obesity, bariatric surgeries often induce a robust and rapid weight-independent improvement in glucose homeostasis within days. Early diabetes remission following bariatric surgery is hypothesized to be mediated by rapid alterations in the gut microbiome and bile acids composition, however, the exact mechanism is yet to be uncovered. Elucidating this mechanism is important as it may form the basis of a new therapeutic modality in diabetes. The investigators intend to deeply characterize early post-bariatric changes in the gut microbiome of diabetic patients, as well as their gut mucosal transcriptome and metabolome, by using state-of-the-art experimental and computational pipelines. Additionally, The investigators will utilize a unique mouse model of bariatric surgery under germ-free conditions, developed at the Elinav lab, that allows us to dissect the role of microbes in post-operative metabolic improvements.
Read the detailed description
Type 2 diabetes mellitus (T2DM) is one of the most prevalent and deadly conditions in the 21st century. T2DM is characterized by obesity and insulin resistance that leads to chronic hyperglycemia, which even with best medical care is often uncontrolled, resulting in life-threatening micro- and macrovascular complications.
The gut microbiota (i.e. the microbial population inhabiting the gut) has been extensively linked to blood glucose levels and was shown to mediate insulin response in various settings, including anti-diabetic pharmacotherapy. Moreover, fecal microbial transplantation (FMT) from lean healthy donors improved insulin resistance in humans suffering from metabolic syndrome. These pre-clinical and clinical evidence suggest that the gut microbiota has a mechanistic role in insulin-resistance.
Bariatric surgeries were originally designed to treat obesity but were also retrospectively found to ameliorate T2DM among other metabolic and non-metabolic disorders. Since obesity is a significant risk factor for T2DM, it is not surprising that surgically-induced weight loss which occurs within several months after surgery also improves insulin sensitivity. However, a substantial share of patients experience an improvement in insulin resistance within days after bariatric surgery, which clinically presents as normal glycemic values despite decreased dosage of anti-diabetic medications in the first post-operative days. This phenomenon of early diabetes remission after surgery precedes any weight-loss, therefore it is weight-independent and it is far from being understood.
Several explanations were suggested to explain early post-bariatric surgery diabetes remission, among which are acute caloric restriction, amplified incretins response, and rapid alterations in bile acids composition; however, none of them accounts for such a drastic improvement in glycemic control within such a short time frame.
Bariatric surgery rapidly alters the gut microbiome in a conserved fashion in both humans and rodents. Although descriptive studies demonstrated a change in microbiome composition within a few months after surgery, most studies didn't analyze microbiome in the first post-operative weeks in which the improvement in diabetes takes place, and data so far remains associative at best. Two independent studies exhibited improved metabolism following FMT from post-bariatric surgery humans and mice donors
into germ-free (microbiota-devoid) mice recipients, however, no mechanism was suggested and both studies used stool samples taken at a very late postoperative period, therefore no conclusions could be made regarding early diabetic remission. Caloric restriction, incretins, bile-acids, and the gut microbiome most probably "co-evolve" following surgery to exert surgery's beneficial metabolic effect with no single factor solely responsible for the entire effect.
Despite being highly effective in ameliorating obesity and obesity-related co-morbidities in the short-term, bariatric surgeries are invasive, risky, and not always successful in the long-term. Bariatric surgeries are thus far from being a perfect solution to obese diabetic patients, but they do serve as an intriguing investigational-model in the context of glucose metabolism. Hopefully, probing the mechanisms behind surgery's metabolic effect will facilitate the development of safer treatments for diabetic patients.
- Conditions
- Diabetes Mellitus, Bariatric Surgery Candidate
- Being tested
- Continuous Glucose monitoring in the perioperative period
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuous Glucose monitoring in the perioperative periodDiagnostic test
All participants will undergo medical and metabolic profiling before surgery at baseline, and during the first two weeks following surgery. Metabolic profiling will take place during a run-in session in the Sheba medical center, that will include (A) A detailed briefing on study design, goals, samples collection and OGTT, as well as home sample-collecting kit distribution (B) Installation of a continuous glucose monitoring system (CGM, Abbott 'freeStyle Libre').
| Study group | Role | What they receive |
|---|---|---|
| Bariatric Surgery Candidates | Experimental | All participants will undergo medical and metabolic profiling before surgery at baseline, and during the first two weeks following surgery. Metabolic profiling will take place during a run-in session in the Sheba medical center, that will include (A) A detailed briefing on study design, goals, samples collection and OGTT, as well as home sample-collecting kit distribution (B) Installation of a continuous glucose monitoring system (CGM, Abbott 'freeStyle Libre'). Receives: Diagnostic Test: Continuous Glucose monitoring in the perioperative period |
| Laparoscopy Cholecystectomy | Sham comparator | All participants will undergo medical and metabolic profiling before surgery at baseline, and during the first two weeks following surgery. Metabolic profiling will take place during a run-in session in the Sheba medical center, that will include (A) A detailed briefing on study design, goals, samples collection and OGTT, as well as home sample-collecting kit distribution (B) Installation of a continuous glucose monitoring system (CGM, Abbott 'freeStyle Libre'). Receives: Diagnostic Test: Continuous Glucose monitoring in the perioperative period |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in intestinal microbiota composition prior and following bariatric surgery
Changes in intestinal microbiota composition following bariatric surgery measured with RNA sequencing
Measured: two weeks
Changes in glycemic index prior and following bariatric surgery
Changes in glycemic index prior and following bariatric surgery measured with continues glucose monitoring system (FreeStyle Libre)
Measured: two weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2020
- Study start1 Mar 2020 (estimated)
- Primary completion1 Jan 2022 (estimated)
- Study completion1 Aug 2022 (estimated)
Why it stopped: No participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Sheba Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Bariatric surgery candidates for two types of bariatric surgery, i.e. sleeve gastrectomy (n=80) and Roux-en-Y gastric bypass (RYGB, n=80) will be recruited to the study from the bariatric surgery clinic in the Sheba medical center and will be followed pre- and postoperatively. A control group of candidates for another non-bariatric upper-GI surgery, i.e. cholecystectomy (n=80), will be recruited as well. All participants will undergo medical and metabolic profiling before surgery at baseline, and during the first two weeks following surgery. Metabolic profiling will take place during a run-in session in the Sheba medical center, that will include (A) A detailed briefing on study design, goals, samples collection and OGTT, as well as home sample-collecting kit distribution (B) Installation of a continuous glucose monitoring system (CGM, Abbott 'freeStyle Libre').
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheba Medical Center
- Sponsor type
- Other government
- Collaborators
- Weizmann Institute of Science
- Responsible party
- Principal investigator, Dr. Nir Horesh resident Department of Surgery and Transplant, Sheba Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04263168
- Sponsor's protocol ID
- 6397-19-SMC
- Status last verified
- Oct 2021
- First submitted
- 19 Oct 2019
- Last updated
- 11 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glycemic Index Variations In the Early Period Following Bariatric Surgery
- ClinicalTrials.gov ID
- NCT04263168
- Acronym / sponsor ID
- 6397-19-SMC
- Conditions
- Diabetes Mellitus, Bariatric Surgery Candidate
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Sheba Medical CenterOther government
- Collaborators
- Weizmann Institute of Science
- Study start
- 1 Mar 2020 (estimated)
- Primary completion
- 1 Jan 2022 (estimated)
- Study completion
- 1 Aug 2022 (estimated)
- First posted
- 10 Feb 2020 (actual)
- 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 diverse community of gut microbes commonly referred to as the 'gut microbiome', is increasingly suggested to play significant roles in health and disease, and to affect even distant non-GI organs by metabolite signaling. Type 2 diabetes mellitus (T2DM) patients feature a distinct gut microbiome signature4, while modulating the gut microbiome by either antibiotics or fecal microbial transplantation (FMT) is suggested to impact insulin sensitivity. Originally designed to treat obesity, bariatric surgeries often induce a robust and rapid weight-independent improvement in glucose homeostasis within days. Early diabetes remission following bariatric surgery is hypothesized to be mediated by rapid alterations in the gut microbiome and bile acids composition, however, the exact mechanism is yet to be uncovered. Elucidating this mechanism is important as it may form the basis of a new therapeutic modality in diabetes. The investigators intend to deeply characterize early post-bariatric changes in the gut microbiome of diabetic patients, as well as their gut mucosal transcriptome and metabolome, by using state-of-the-art experimental and computational pipelines. Additionally, The investigators will utilize a unique mouse model of bariatric surgery under germ-free conditions, developed at the Elinav lab, that allows us to dissect the role of microbes in post-operative metabolic improvements.
Detailed description
Type 2 diabetes mellitus (T2DM) is one of the most prevalent and deadly conditions in the 21st century. T2DM is characterized by obesity and insulin resistance that leads to chronic hyperglycemia, which even with best medical care is often uncontrolled, resulting in life-threatening micro- and macrovascular complications.
The gut microbiota (i.e. the microbial population inhabiting the gut) has been extensively linked to blood glucose levels and was shown to mediate insulin response in various settings, including anti-diabetic pharmacotherapy. Moreover, fecal microbial transplantation (FMT) from lean healthy donors improved insulin resistance in humans suffering from metabolic syndrome. These pre-clinical and clinical evidence suggest that the gut microbiota has a mechanistic role in insulin-resistance.
Bariatric surgeries were originally designed to treat obesity but were also retrospectively found to ameliorate T2DM among other metabolic and non-metabolic disorders. Since obesity is a significant risk factor for T2DM, it is not surprising that surgically-induced weight loss which occurs within several months after surgery also improves insulin sensitivity. However, a substantial share of patients experience an improvement in insulin resistance within days after bariatric surgery, which clinically presents as normal glycemic values despite decreased dosage of anti-diabetic medications in the first post-operative days. This phenomenon of early diabetes remission after surgery precedes any weight-loss, therefore it is weight-independent and it is far from being understood.
Several explanations were suggested to explain early post-bariatric surgery diabetes remission, among which are acute caloric restriction, amplified incretins response, and rapid alterations in bile acids composition; however, none of them accounts for such a drastic improvement in glycemic control within such a short time frame.
Bariatric surgery rapidly alters the gut microbiome in a conserved fashion in both humans and rodents. Although descriptive studies demonstrated a change in microbiome composition within a few months after surgery, most studies didn't analyze microbiome in the first post-operative weeks in which the improvement in diabetes takes place, and data so far remains associative at best. Two independent studies exhibited improved metabolism following FMT from post-bariatric surgery humans and mice donors
into germ-free (microbiota-devoid) mice recipients, however, no mechanism was suggested and both studies used stool samples taken at a very late postoperative period, therefore no conclusions could be made regarding early diabetic remission. Caloric restriction, incretins, bile-acids, and the gut microbiome most probably "co-evolve" following surgery to exert surgery's beneficial metabolic effect with no single factor solely responsible for the entire effect.
Despite being highly effective in ameliorating obesity and obesity-related co-morbidities in the short-term, bariatric surgeries are invasive, risky, and not always successful in the long-term. Bariatric surgeries are thus far from being a perfect solution to obese diabetic patients, but they do serve as an intriguing investigational-model in the context of glucose metabolism. Hopefully, probing the mechanisms behind surgery's metabolic effect will facilitate the development of safer treatments for diabetic patients.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Bariatric surgery candidates for two types of bariatric surgery, i.e. sleeve gastrectomy (n=80) and Roux-en-Y gastric bypass (RYGB, n=80) will be recruited to the study from the bariatric surgery clinic in the Sheba medical center and will be followed pre- and postoperatively. A control group of candidates for another non-bariatric upper-GI surgery, i.e. cholecystectomy (n=80), will be recruited as well. All participants will undergo medical and metabolic profiling before surgery at baseline, and during the first two weeks following surgery. Metabolic profiling will take place during a run-in session in the Sheba medical center, that will include (A) A detailed briefing on study design, goals, samples collection and OGTT, as well as home sample-collecting kit distribution (B) Installation of a continuous glucose monitoring system (CGM, Abbott 'freeStyle Libre').
| Arm | Type | Receives |
|---|---|---|
| Bariatric Surgery Candidates | Experimental | Diagnostic Test: Continuous Glucose monitoring in the perioperative periodAll participants will undergo medical and metabolic profiling before surgery at baseline, and during the first two weeks following surgery. Metabolic profiling will take place during a run-in session in the Sheba medical center, that will include (A) A detailed briefing on study design, goals, samples collection and OGTT, as well as home sample-collecting kit distribution (B) Installation of a continuous glucose monitoring system (CGM, Abbott 'freeStyle Libre'). |
| Laparoscopy Cholecystectomy | Sham comparator | Diagnostic Test: Continuous Glucose monitoring in the perioperative periodAll participants will undergo medical and metabolic profiling before surgery at baseline, and during the first two weeks following surgery. Metabolic profiling will take place during a run-in session in the Sheba medical center, that will include (A) A detailed briefing on study design, goals, samples collection and OGTT, as well as home sample-collecting kit distribution (B) Installation of a continuous glucose monitoring system (CGM, Abbott 'freeStyle Libre'). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult Population (> 18 years old)
- Diabetic Patients (Type 2)
- Bariatric surgery candidates for two types of bariatric surgery, i.e. sleeve gastrectomy and Roux-en-Y gastric bypass
- Laparoscopic Cholecystectomy candidates
Key exclusion criteria (2 listed)
- Pregnant Women
- < 18 years old
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 |
|---|---|---|
| Continuous Glucose monitoring in the perioperative periodAll participants will undergo medical and metabolic profiling before surgery at baseline, and during the first two weeks following surgery. Metabolic profiling will take place during a run-in session in the Sheba medical center, that will include (A) A detailed briefing on study design, goals, samples collection and OGTT, as well as home sample-collecting kit distribution (B) Installation of a continuous glucose monitoring system (CGM, Abbott 'freeStyle Libre'). | Diagnostic test | Bariatric Surgery Candidates, Laparoscopy Cholecystectomy |
Primary outcome
Changes in intestinal microbiota composition prior and following bariatric surgery
Time frame: two weeks
Changes in intestinal microbiota composition following bariatric surgery measured with RNA sequencing
Changes in glycemic index prior and following bariatric surgery
Time frame: two weeks
Changes in glycemic index prior and following bariatric surgery measured with continues glucose monitoring system (FreeStyle Libre)
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 11 Oct 2021.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Continuous Glucose monitoring in the perioperative period in people with Diabetes Mellitus and Bariatric Surgery Candidate, run by Sheba Medical Center at 1 site in Israel.
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 4 inclusion and 2 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 11 Oct 2021. 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 Israel. 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.
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?
Changes in intestinal microbiota composition prior and following bariatric surgery (time frame: two weeks). The study lists 2 primary outcomes in all. 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 11 Oct 2021.