Type 2 DiabetesPhase 1NCT02913703
Preprandial Ghrelin Effect
A Phase 1 study testing Ghrelin and Saline in people with Type 2 Diabetes, run by Jenny Tong, MD, MPH at 1 site in United States.
Trial summary
Background and Significance: The peptide hormone ghrelin drives hunger and feeding behavior, making it a focus of obesity research. Released mainly by the stomach and proximal small intestine, ghrelin peaks prior to meals, potentially priming the gut for anticipated nutrients. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Ghrelin and Saline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Jan 2017to Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- T2DM study subjects must meet the following inclusion criteria:
- established T2DM with good to moderate glycemic control (HbA1c ≤ 8.5%)
- Diabetes treated with oral medications or lifestyle management
- BMI 25.0 - 45.0 kg/m2
- Healthy control subjects must meet the following inclusion criteria:
- Fasting glucose <100 mg/dL, as measured at screening visit
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- HbA1c < 5.7%, as measured at screening visit
- BMI 18.0 - 29.9 kg/m2
- No diagnosis of diabetes mellitus (including gestational diabetes)
- Age between 18 - 40 years
Who cannot join
- All subjects will be excluded for the following reasons:
- Active infections
- History of malignant or inflammatory conditions, such as rheumatoid arthritis and inflammatory bowel disease
- History of myocardial infarction or congestive heart failure
- History or active liver or renal disease (AST or ALT >2x upper limits of normal, calculated glomerular filtration rate [eGFR] <60 at screening)
- Anemia defined as hematocrit <34% at screening visit
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- Uncontrolled hypertension
- History of pituitary or adrenal disorders or neuroendocrine tumor
- History of anorexia nervosa or previous gastrointestinal surgery
- Malabsorptive GI disease, such as celiac disease
- Pregnancy or lactation
- Use of medications that alter glucose metabolism or GI function (glucocorticoids, psychotropics, niacin, narcotic, metoclopramide)
- Use of insulin or GLP-1 based therapy (i.e. DPP-4 inhibitors, GLP-1 receptor agonists)
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke Center For Living
Durham, North Carolina, 27705
About this study
Official title: Effect of Preprandial Ghrelin on Postprandial Glucose Tolerance
Background and Significance: The peptide hormone ghrelin drives hunger and feeding behavior, making it a focus of obesity research. Released mainly by the stomach and proximal small intestine, ghrelin peaks prior to meals, potentially priming the gut for anticipated nutrients. After eating, ghrelin abruptly declines, with levels varying 2- to 3-fold between the fasted and fed states. Interestingly, in obesity and type 2 diabetes (T2D), this pattern is disrupted. Individuals with these disorders have chronically suppressed ghrelin levels and little variation before and after meals.
Although ghrelin's preprandial rise and postprandial fall is a well-established phenomenon, its role in regulating glucose metabolism is unclear. In mice, increasing preprandial ghrelin levels improves glucose tolerance through enhanced glucagon-like peptide-1 (GLP-1) secretion. Ghrelin also stimulates GLP-1 secretion from mouse and human intestinal L-cells in vitro. These findings suggest enhanced postprandial GLP-1 as a novel role for the preprandial ghrelin surge. A ghrelin-incretin enteroendocrine axis could also explain the poor postprandial GLP-1 secretion and glucose tolerance in subjects with T2D, given their preprandial hypoghrelinemia.
Read more
The investigators' preliminary data demonstrate that in humans, increasing circulating ghrelin to a supraphysiologic range worsened glucose tolerance, despite increased GLP-1 secretion. The discrepancy between these findings and the ones from rodents could be due to difference in study design and/or species. For example, the investigators' study used a continuous ghrelin infusion, which resulted in elevated levels of ghrelin pre- and postprandially. Elevated postprandial ghrelin likely mitigated the positive effects of increased GLP-1 secretion by raising levels of glucagon and other counter-regulatory hormones.
This study seeks to delineate the interactions between ghrelin and GLP-1 in the regulation of glucose tolerance, beta-cell function, and insulin sensitivity. The investigators hypothesize that increased preprandial ghrelin will enhance GLP-1 secretion and consequently improve glucose tolerance in healthy subjects and those with T2D. Confirmation of these hypotheses would advance the investigators understanding of the control of glucose homeostasis and have important clinical and therapeutic implications. Modulating ghrelin levels may provide a novel therapeutic strategy to improve glucose tolerance in individuals with T2D, which affects an estimated 350 million people worldwide.
- Conditions
- Type 2 Diabetes
- Being tested
- Ghrelin, Saline
- Keywords
- Ghrelin
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GhrelinDrug
Boluses of Ghrelin will be given over a 1 minute period at 3 ug/kg. Ensure (2 cans) will also be given.
SalineOther
Boluses of saline will be given over a 1 minute period. Ensure (2 cans) will also be given.
| Study group | Role | What they receive |
|---|---|---|
| Healthy subjects - Preprandial AG (Acyl Ghrelin) | Experimental | Control group of healthy subjects. Subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial AG (Acyl Ghrelin) bolus over 1 minute. Sixty minutes later, they will receive a liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. Receives: Drug: Ghrelin |
| Healthy subjects - Preprandial saline | Experimental | Control group of healthy subjects. Subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial saline bolus over 1 minute. Sixty minutes later, they will receive a liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. Receives: Other: Saline |
| Healthy subjects - Prandial AG | Experimental | Control group of healthy subjects. Subjects will eat standardized, provided breakfast at home; then after a 5 hour fast, they will receive a prandial AG bolus over 1 minute starting at the same time as the liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. Receives: Drug: Ghrelin |
| Healthy subjects - Preprandial & prandial AG | Experimental | Control group of healthy subjects. Subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial AG bolus over 1 minute. Sixty minutes later, they will receive another AG bolus over 1 minute starting at the same time as the liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. Receives: Drug: Ghrelin |
| Diabetic subjects - Preprandial AG | Experimental | Type 2 diabetic subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial AG bolus over 1 minute. Sixty minutes later, they will receive a liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. Receives: Drug: Ghrelin |
| Diabetic subjects - Preprandial Saline | Experimental | Type 2 diabetic subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial saline bolus over 1 minute. Sixty minutes later, they will receive a liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. Receives: Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effect of preprandial ghrelin on glucose tolerance
Primary Outcome: Glucose area under the curve during 60-minute Meal Tolerance test in healthy subjects and in Type 2 diabetic subjects
Measured: Approximately 4-8 weeks
Secondary outcomes (4)
Effect of preprandial ghrelin on GLP-1 secretion
Secondary Outcome: Effect of preprandial ghrelin on GLP-1 area under the curve during a mixed meal in healthy subjects and in Type 2 diabetic subjects
Measured: Approx 4-8 weeks
Effect of preprandial ghrelin on insulin secretion
Secondary Outcome: Effect of preprandial ghrelin on insulin and c-peptide area under the curve during a mixed meal in healthy subjects and in Type 2 diabetic subjects
Measured: Approx 4-8 weeks
Effect of preprandial ghrelin on beta cell function
Secondary Outcome: Effect of preprandial ghrelin on beta cell function (as measured by Disposition Index = [ (Area under the insulin curve / Area under the glucose curve) X Matsuda Index] during a 60-minute Meal Tolerance test in healthy subjects and in Type 2 diabetic subjects
Measured: Approx 4-8 weeks
Effect of preprandial ghrelin on insulin sensitivity (as measured by Matsuda index)
Measured: Approx 4-8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Sep 2016 (estimated)
- Study start11 Jan 2017
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jenny Tong, MD, MPH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jenny Tong, MD, MPH, Duke University
- Investigators
- Jenny Tong, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02913703
- Sponsor's protocol ID
- Pro00071271
- Other IDs
- R01DK097550
- Status last verified
- Jul 2018
- First submitted
- 22 Sep 2016
- Last updated
- 12 Mar 2019
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Preprandial Ghrelin on Postprandial Glucose Tolerance
- ClinicalTrials.gov ID
- NCT02913703
- Acronym / sponsor ID
- Pro00071271
- Conditions
- Type 2 Diabetes
- Keywords
- Ghrelin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Jenny Tong, MD, MPHUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 11 Jan 2017 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 26 Sep 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.
Background and Significance: The peptide hormone ghrelin drives hunger and feeding behavior, making it a focus of obesity research. Released mainly by the stomach and proximal small intestine, ghrelin peaks prior to meals, potentially priming the gut for anticipated nutrients. After eating, ghrelin abruptly declines, with levels varying 2- to 3-fold between the fasted and fed states. Interestingly, in obesity and type 2 diabetes (T2D), this pattern is disrupted. Individuals with these disorders have chronically suppressed ghrelin levels and little variation before and after meals.
Although ghrelin's preprandial rise and postprandial fall is a well-established phenomenon, its role in regulating glucose metabolism is unclear. In mice, increasing preprandial ghrelin levels improves glucose tolerance through enhanced glucagon-like peptide-1 (GLP-1) secretion. Ghrelin also stimulates GLP-1 secretion from mouse and human intestinal L-cells in vitro. These findings suggest enhanced postprandial GLP-1 as a novel role for the preprandial ghrelin surge. A ghrelin-incretin enteroendocrine axis could also explain the poor postprandial GLP-1 secretion and glucose tolerance in subjects with T2D, given their preprandial hypoghrelinemia.
The investigators' preliminary data demonstrate that in humans, increasing circulating ghrelin to a supraphysiologic range worsened glucose tolerance, despite increased GLP-1 secretion. The discrepancy between these findings and the ones from rodents could be due to difference in study design and/or species. For example, the investigators' study used a continuous ghrelin infusion, which resulted in elevated levels of ghrelin pre- and postprandially. Elevated postprandial ghrelin likely mitigated the positive effects of increased GLP-1 secretion by raising levels of glucagon and other counter-regulatory hormones.
This study seeks to delineate the interactions between ghrelin and GLP-1 in the regulation of glucose tolerance, beta-cell function, and insulin sensitivity. The investigators hypothesize that increased preprandial ghrelin will enhance GLP-1 secretion and consequently improve glucose tolerance in healthy subjects and those with T2D. Confirmation of these hypotheses would advance the investigators understanding of the control of glucose homeostasis and have important clinical and therapeutic implications. Modulating ghrelin levels may provide a novel therapeutic strategy to improve glucose tolerance in individuals with T2D, which affects an estimated 350 million people worldwide.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Healthy subjects - Preprandial AG (Acyl Ghrelin) | Experimental | Drug: GhrelinControl group of healthy subjects. Subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial AG (Acyl Ghrelin) bolus over 1 minute. Sixty minutes later, they will receive a liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. |
| Healthy subjects - Preprandial saline | Experimental | Other: SalineControl group of healthy subjects. Subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial saline bolus over 1 minute. Sixty minutes later, they will receive a liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. |
| Healthy subjects - Prandial AG | Experimental | Drug: GhrelinControl group of healthy subjects. Subjects will eat standardized, provided breakfast at home; then after a 5 hour fast, they will receive a prandial AG bolus over 1 minute starting at the same time as the liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. |
| Healthy subjects - Preprandial & prandial AG | Experimental | Drug: GhrelinControl group of healthy subjects. Subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial AG bolus over 1 minute. Sixty minutes later, they will receive another AG bolus over 1 minute starting at the same time as the liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. |
| Diabetic subjects - Preprandial AG | Experimental | Drug: GhrelinType 2 diabetic subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial AG bolus over 1 minute. Sixty minutes later, they will receive a liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. |
| Diabetic subjects - Preprandial Saline | Experimental | Other: SalineType 2 diabetic subjects will eat standardized, provided breakfast at home; then after a 4 hour fast, they will receive a preprandial saline bolus over 1 minute. Sixty minutes later, they will receive a liquid mixed meal (Ensure: 2 cans/474 ml). Venous blood samples will be taken over the entire 245 minutes. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- established T2DM with good to moderate glycemic control (HbA1c ≤ 8.5%)
- Diabetes treated with oral medications or lifestyle management
- BMI 25.0 - 45.0 kg/m2
- Fasting glucose <100 mg/dL, as measured at screening visit
- HbA1c < 5.7%, as measured at screening visit
Key exclusion criteria (13 listed)
- Active infections
- History of malignant or inflammatory conditions, such as rheumatoid arthritis and inflammatory bowel disease
- History of myocardial infarction or congestive heart failure
- History or active liver or renal disease (AST or ALT >2x upper limits of normal, calculated glomerular filtration rate [eGFR] <60 at screening)
- Anemia defined as hematocrit <34% at screening visit
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 |
|---|---|---|
| GhrelinBoluses of Ghrelin will be given over a 1 minute period at 3 ug/kg. Ensure (2 cans) will also be given. | Drug | Diabetic subjects - Preprandial AG, Healthy subjects - Prandial AG, Healthy subjects - Preprandial & prandial AG, Healthy subjects - Preprandial AG (Acyl Ghrelin) |
| SalineBoluses of saline will be given over a 1 minute period. Ensure (2 cans) will also be given. | Other | Diabetic subjects - Preprandial Saline, Healthy subjects - Preprandial saline |
Primary outcome
Effect of preprandial ghrelin on glucose tolerance
Time frame: Approximately 4-8 weeks
Primary Outcome: Glucose area under the curve during 60-minute Meal Tolerance test in healthy subjects and in Type 2 diabetic subjects
4 secondary outcomes
Effect of preprandial ghrelin on GLP-1 secretion
Time frame: Approx 4-8 weeks
Effect of preprandial ghrelin on insulin secretion
Time frame: Approx 4-8 weeks
Effect of preprandial ghrelin on beta cell function
Time frame: Approx 4-8 weeks
Effect of preprandial ghrelin on insulin sensitivity (as measured by Matsuda index)
Time frame: Approx 4-8 weeks
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 12 Mar 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.
Jenny Tong, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ghrelin and Saline in people with Type 2 Diabetes, run by Jenny Tong, MD, MPH 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 10 inclusion and 13 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 12 Mar 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 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Effect of preprandial ghrelin on glucose tolerance (time frame: Approximately 4-8 weeks). 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 12 Mar 2019.