ObesityNCT01865760
Etiology, Assessment and Treatment of Post-gastric Bypass Severe Hypoglycemia
A study testing Oral Glucose tolerance test (OGGT), Liquid mixed meal and Octreotide in people with Obesity and Hypoglycemia, run by University of Aarhus at 1 site in Denmark.
Trial summary
With increasing rates of obesity the number of anti-obesity operations performed is increasing; one of the most common is gastric bypass. Anti-obesity surgery ameliorates diabetes and several other serious comorbidities, but bariatric surgery is also associated with medical and nutritional complications. Read more about this study
- Who is it for?
- Ages 20 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Hypoglycemia, Surgery
- What is being tested?
- Oral Glucose tolerance test (OGGT), Liquid mixed meal and Octreotide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 33 participants
- Where
- 1 siteDenmark
- Study dates
- Jun 2013to Mar 2016
- 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 20 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male/female
- Legally competent (habil)
- Age 20-65 years
- Speak and understand Danish
- Written consent
- Investigators verification of suitability
Who cannot join
- Heart, liver or kidney disease
- Treatment with Cortisol
- Current treatment with antidiabetic medication
- Epilepsy
- Abuse/addiction to drugs
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Department of Endocrinology, Aarhus University Hospital
Aarhus C, 8000
About this study
Official title: Incidence of Medical and Nutritional Complications After Bariatric Surgery, Especially Focusing on Assessment and Treatment of Severe Hypoglycemia
With increasing rates of obesity the number of anti-obesity operations performed is increasing; one of the most common is gastric bypass. Anti-obesity surgery ameliorates diabetes and several other serious comorbidities, but bariatric surgery is also associated with medical and nutritional complications.
Post-gastric bypass hyperinsulinemic hypoglycemia is a relative rare but serious complication often seen months to years after gastric bypass surgery. The patients experience neuroglycopenic symptoms (eg. inability to concentrate, weakness, altered mental status, loss of consciousness).
The purpose of this study is to determine whether glucagon-like peptide-1 (GLP-1)or other enteropancreatic factors (eg. gastric emptying rate) are responsible for the excessed insulin secretion seen in some patients after bariatric surgery.
Read the detailed description
The increasing prevalence of obesity has led to parallel increase in bariatric surgery. Sustained weight reductions of up to 50 % of excess body weight are achieved in the majority of patients, and bariatric surgery is more effective in producing sustained weight loss. Another remarkable effect of bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the profound and durable resolution of clinical manifestations of type 2 diabetes. Despite the favorable effects of bariatric surgery on obesity-associated morbidity and mortality, there has been mounting concerns about severe hypoglycemia associated with Roux-en-Y gastric bypass surgery.
This is an increasingly recognized condition characterized by neuroglycopenia and inappropriately elevated insulin concentrations. The patients experience autonomic symptoms with tremor, palpitation, sweating and hunger, and symptoms of neuroglycopenia such as inability to concentrate, weakness, drowsiness and behavioral changes. One issue complicating the characterization of post-gastric bypass surgery is that patients who have undergone bariatric surgery typically experience numerous post-prandial symptoms including the "dumping syndrome", which may be part of a continuum of post-gastric bypass hypoglycemia. We know that affected individuals have exaggerated insulin and glucagon-like peptide-1 response to meal consumption compared with asymptomatic individuals with prior gastric bypass surgery.
Ten patients with recurrent hypoglycemia events, including the presence of Whipple's triad, following gastric bypass surgery will participate in this study. Ten asymptomatic subjects with previous gastric bypass surgery and 10 control subjects with normal glucose tolerance and no prior gastrointestinal surgery will be recruited. Ten subjects with prior sleeve-gastrectomi will also participate in order to see if this operation is more beneficial in avoiding post-gastric bypass hypoglycemia.
Pre- and postprandial hormone levels and insulin secretion rates in response to 50 mg oral glucose tolerance test (OGTT), isoglycemic intravenous glucose infusion (IIGI) and 300 kcal liquid mixed meal will be measured in 3 different days separated by an interval of at least 1 week. These tests will be performed to see how the response to intravenous versus per oral glucose stimulation differ in the four different groups in regard to biomedical markers and symptoms of hypoglycemia.
All participants will wear Continuous Glucose Monitoring (CGM) for at least 5 days. During this period of time the subjects will be asked to come to the laboratory on two separate days to receive a high-carbohydrate meal and a low-carbohydrate meal respectively. The ingestion of the will be followed by three hours blood glucose measurements along with the CGM. The purpose of these test are to see the different response in glucose depending on the composition of the meal ingested, and to see whether CGM is reliably especially for measuring low levels of glucose.
The subjects with recurrent hypoglycemia events following gastric bypass surgery will receive the liquid mixed meal three times separated by at least one week; first as described earlier without receiving any drug and afterwards receiving either Exendin 9-39 (a specific GLP-1 receptor antagonist) or a Octreotid (Somatostatin analog). The purpose of these tests are to test the hypothesis that gastric bypass surgery associated hyperinsulinemic hypoglycemia is mediated by increased GLP-1 actions. Furthermore we use the somatostatin analog to test whether an inhibition of other gastroenteropancreatic hormones and a delay in gastric emptying of solids will change the glucose-insulin metabolism. To evaluate the impact of these pharmacologically interventions on gastric emptying rate we use acetaminophen absorption test.
Aim:
- Is GLP-1 or other gastroenteropancreatic hormones pathophysiologically involved in the development of post-gastric bypass hyperinsulinemic hypoglycemia?
- To investigate whether CGM can be used to diagnose hypoglycemia after gastric bypass surgery?
- Which nutritional and pharmacological options do we have in managing the treatment of this condition?
- Conditions
- Obesity, Hypoglycemia, Surgery
- Being tested
- Oral Glucose tolerance test (OGGT), Liquid mixed meal, Octreotide
- Keywords
- Glucagon like peptide 1, Insulin secretion, Hypoglycemia
- Medical subject headings
- Obesity, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Glucose tolerance test (OGGT)Dietary supplement
At baseline subjects will consume 50 g glucose dissolved in water in 10 minutes
Liquid mixed mealDietary supplement
Also called Liquid mixed meal containing carbohydrate, fat and proteins
At baseline subject will consume the liquid mixed meal in 10 minutes
OctreotideDrug
Also called Somatostatin analogue
At baseline subjects will receive Octreotid 100 µg subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| Gastric bypass surgery, hypoglycemia | Experimental | Subjects with previous gastric bypass surgery (more then 1 year ago) and symptomatic hypoglycemia according to Whipples triade. These subjects will undergo an oral glucose tolerance test (OGGT), an isoglycemic intravenous glucose infusion (IIGI) and a 300 kcal liquid mixed meal. They will furthermore undergo two additional liquid mixed meal; one with concomitant treatment with synthetic Exendin 9-39 and another with treatment with Octreotide. All tests will be separated by at least one week. Receives: Dietary Supplement: Oral Glucose tolerance test (OGGT); Dietary Supplement: Liquid mixed meal; Drug: Octreotide |
| Gastric bypass surgery, asymptomatic | Active comparator | Subjects with previous gastric bypass surgery (more then 1 year ago) without any signs of hypoglycemia. These subjects will undergo an oral glucose tolerance test (OGGT), an isoglycemic intravenous glucose infusion (IIGI) and a 300 kcal liquid mixed meal. Receives: Dietary Supplement: Oral Glucose tolerance test (OGGT); Dietary Supplement: Liquid mixed meal |
| Controls | Other | Healthy non-operated control subjects, matched on BMI, age and sex. These subjects will undergo an oral glucose tolerance test (OGGT), an isoglycemic intravenous glucose infusion (IIGI) and a 300 kcal liquid mixed meal. Receives: Dietary Supplement: Oral Glucose tolerance test (OGGT); Dietary Supplement: Liquid mixed meal |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in biomedical markers (eg. blood glucose) in response to a liquid meal.
Measured: Baseline 30 minutes and just before meal ingestion. Biomedical markers will be monitored continuously in 5 hours after meal ingestion
Secondary outcomes (1)
Continuous Glucose Monitoring as an indicator of post-gastric bypass hypoglycemia
We will evaluate the degree of hypoglycemia by the following parameters:
- percent time spent per dag with hypoglycemia (glucose ≤ 3,89 mmol/L)
- excursions during which interstitial glucose will fall below 3,89 mmol/l per day
- average minimum interstitial glucose values
Measured: Monitoring for five days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2013 (estimated)
- Study startJun 2013
- Primary completionMar 2016
- Study completionMar 2016
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 AarhusThe 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Region MidtJylland Denmark
- Responsible party
- Sponsor
- Investigators
- Bjørn Richelsen, Professor, Principal investigator, The department of Endokrinology, Aarhus University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01865760
- Sponsor's protocol ID
- 1-16-02-138-13
- Status last verified
- Dec 2015
- First submitted
- 15 May 2013
- Last updated
- 28 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Incidence of Medical and Nutritional Complications After Bariatric Surgery, Especially Focusing on Assessment and Treatment of Severe Hypoglycemia
- ClinicalTrials.gov ID
- NCT01865760
- Acronym / sponsor ID
- 1-16-02-138-13
- Conditions
- Obesity, Hypoglycemia, Surgery
- Keywords
- Glucagon like peptide 1, Insulin secretion, Hypoglycemia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Region MidtJylland Denmark
- Study start
- Jun 2013
- Primary completion
- Mar 2016 (actual)
- Study completion
- Mar 2016 (actual)
- First posted
- 31 May 2013 (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.
With increasing rates of obesity the number of anti-obesity operations performed is increasing; one of the most common is gastric bypass. Anti-obesity surgery ameliorates diabetes and several other serious comorbidities, but bariatric surgery is also associated with medical and nutritional complications.
Post-gastric bypass hyperinsulinemic hypoglycemia is a relative rare but serious complication often seen months to years after gastric bypass surgery. The patients experience neuroglycopenic symptoms (eg. inability to concentrate, weakness, altered mental status, loss of consciousness).
The purpose of this study is to determine whether glucagon-like peptide-1 (GLP-1)or other enteropancreatic factors (eg. gastric emptying rate) are responsible for the excessed insulin secretion seen in some patients after bariatric surgery.
Detailed description
The increasing prevalence of obesity has led to parallel increase in bariatric surgery. Sustained weight reductions of up to 50 % of excess body weight are achieved in the majority of patients, and bariatric surgery is more effective in producing sustained weight loss. Another remarkable effect of bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the profound and durable resolution of clinical manifestations of type 2 diabetes. Despite the favorable effects of bariatric surgery on obesity-associated morbidity and mortality, there has been mounting concerns about severe hypoglycemia associated with Roux-en-Y gastric bypass surgery.
This is an increasingly recognized condition characterized by neuroglycopenia and inappropriately elevated insulin concentrations. The patients experience autonomic symptoms with tremor, palpitation, sweating and hunger, and symptoms of neuroglycopenia such as inability to concentrate, weakness, drowsiness and behavioral changes. One issue complicating the characterization of post-gastric bypass surgery is that patients who have undergone bariatric surgery typically experience numerous post-prandial symptoms including the "dumping syndrome", which may be part of a continuum of post-gastric bypass hypoglycemia. We know that affected individuals have exaggerated insulin and glucagon-like peptide-1 response to meal consumption compared with asymptomatic individuals with prior gastric bypass surgery.
Ten patients with recurrent hypoglycemia events, including the presence of Whipple's triad, following gastric bypass surgery will participate in this study. Ten asymptomatic subjects with previous gastric bypass surgery and 10 control subjects with normal glucose tolerance and no prior gastrointestinal surgery will be recruited. Ten subjects with prior sleeve-gastrectomi will also participate in order to see if this operation is more beneficial in avoiding post-gastric bypass hypoglycemia.
Pre- and postprandial hormone levels and insulin secretion rates in response to 50 mg oral glucose tolerance test (OGTT), isoglycemic intravenous glucose infusion (IIGI) and 300 kcal liquid mixed meal will be measured in 3 different days separated by an interval of at least 1 week. These tests will be performed to see how the response to intravenous versus per oral glucose stimulation differ in the four different groups in regard to biomedical markers and symptoms of hypoglycemia.
All participants will wear Continuous Glucose Monitoring (CGM) for at least 5 days. During this period of time the subjects will be asked to come to the laboratory on two separate days to receive a high-carbohydrate meal and a low-carbohydrate meal respectively. The ingestion of the will be followed by three hours blood glucose measurements along with the CGM. The purpose of these test are to see the different response in glucose depending on the composition of the meal ingested, and to see whether CGM is reliably especially for measuring low levels of glucose.
The subjects with recurrent hypoglycemia events following gastric bypass surgery will receive the liquid mixed meal three times separated by at least one week; first as described earlier without receiving any drug and afterwards receiving either Exendin 9-39 (a specific GLP-1 receptor antagonist) or a Octreotid (Somatostatin analog). The purpose of these tests are to test the hypothesis that gastric bypass surgery associated hyperinsulinemic hypoglycemia is mediated by increased GLP-1 actions. Furthermore we use the somatostatin analog to test whether an inhibition of other gastroenteropancreatic hormones and a delay in gastric emptying of solids will change the glucose-insulin metabolism. To evaluate the impact of these pharmacologically interventions on gastric emptying rate we use acetaminophen absorption test.
Aim:
- Is GLP-1 or other gastroenteropancreatic hormones pathophysiologically involved in the development of post-gastric bypass hyperinsulinemic hypoglycemia?
- To investigate whether CGM can be used to diagnose hypoglycemia after gastric bypass surgery?
- Which nutritional and pharmacological options do we have in managing the treatment of this condition?
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Gastric bypass surgery, hypoglycemia | Experimental | Dietary Supplement: Oral Glucose tolerance test (OGGT), Dietary Supplement: Liquid mixed meal, Drug: OctreotideSubjects with previous gastric bypass surgery (more then 1 year ago) and symptomatic hypoglycemia according to Whipples triade. These subjects will undergo an oral glucose tolerance test (OGGT), an isoglycemic intravenous glucose infusion (IIGI) and a 300 kcal liquid mixed meal. They will furthermore undergo two additional liquid mixed meal; one with concomitant treatment with synthetic Exendin 9-39 and another with treatment with Octreotide. All tests will be separated by at least one week. |
| Gastric bypass surgery, asymptomatic | Active comparator | Dietary Supplement: Oral Glucose tolerance test (OGGT), Dietary Supplement: Liquid mixed mealSubjects with previous gastric bypass surgery (more then 1 year ago) without any signs of hypoglycemia. These subjects will undergo an oral glucose tolerance test (OGGT), an isoglycemic intravenous glucose infusion (IIGI) and a 300 kcal liquid mixed meal. |
| Controls | Other | Dietary Supplement: Oral Glucose tolerance test (OGGT), Dietary Supplement: Liquid mixed mealHealthy non-operated control subjects, matched on BMI, age and sex. These subjects will undergo an oral glucose tolerance test (OGGT), an isoglycemic intravenous glucose infusion (IIGI) and a 300 kcal liquid mixed meal. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male/female
- Legally competent (habil)
- Age 20-65 years
- Speak and understand Danish
- Written consent
Key exclusion criteria (5 listed)
- Heart, liver or kidney disease
- Treatment with Cortisol
- Current treatment with antidiabetic medication
- Epilepsy
- Abuse/addiction to drugs
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 |
|---|---|---|
| Oral Glucose tolerance test (OGGT)At baseline subjects will consume 50 g glucose dissolved in water in 10 minutes | Dietary supplement | Controls, Gastric bypass surgery, asymptomatic, Gastric bypass surgery, hypoglycemia |
| Liquid mixed mealAlso: Liquid mixed meal containing carbohydrate, fat and proteinsAt baseline subject will consume the liquid mixed meal in 10 minutes | Dietary supplement | Controls, Gastric bypass surgery, asymptomatic, Gastric bypass surgery, hypoglycemia |
| OctreotideAlso: Somatostatin analogueAt baseline subjects will receive Octreotid 100 µg subcutaneous | Drug | Gastric bypass surgery, hypoglycemia |
Primary outcome
Changes in biomedical markers (eg. blood glucose) in response to a liquid meal.
Time frame: Baseline 30 minutes and just before meal ingestion. Biomedical markers will be monitored continuously in 5 hours after meal ingestion
1 secondary outcome
Continuous Glucose Monitoring as an indicator of post-gastric bypass hypoglycemia
Time frame: Monitoring for five days
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 28 Oct 2019.
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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.
Bjørn Richelsen, Professor principal investigator
The department of Endokrinology, Aarhus University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oral Glucose tolerance test (OGGT), Liquid mixed meal and Octreotide in people with Obesity and Hypoglycemia, run by University of Aarhus at 1 site in Denmark.
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 6 inclusion and 5 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 28 Oct 2019. 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 Denmark. 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.
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?
Changes in biomedical markers (eg. blood glucose) in response to a liquid meal. (time frame: Baseline 30 minutes and just before meal ingestion. Biomedical markers will be monitored continuously in 5 hours after meal ingestion). 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 28 Oct 2019.