DiabetesNCT01729299
Ghrelin Effect on Beta Cell Function in Health and Disease
A study testing Exendin (9-39), acyl ghrelin and saline in people with Diabetes, run by David Dalessio at 2 sites in United States.
Trial summary
To determine the role of nutrient status on ghrelin regulation of insulin secretion. We hypothesize that ghrelin and glucagon-like peptide-1 (GLP-1)(both are hormones made in the gut,) have differential effects on β-cell function in the fed state. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes
- What is being tested?
- Exendin (9-39), acyl ghrelin and saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 2 sitesUnited States
- Study dates
- Apr 2013to Apr 2014
- 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 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men and women
- Ages between 18 and 45 years
- BMI between 18 and 29 kg/m2
Who cannot join
- History or clinical evidence of impaired fasting glucose or diabetes mellitus, myocardial infarction within the past year, history or symptoms of congestive heart failure, uncontrolled hypertension, history or active liver or renal disease (AST or ALT >2x upper limits of normal, calculated glomerular filtration rate [GFR] <60).
- History of pituitary or adrenal disorders or neuroendocrine tumor.
- Anemia defined as hematocrit <33%.
- Use of medications that alter glucose metabolism
- Pregnancy or lactation.
- Abnormal Electrocardiogram (ECG): evidence of ischemia or arrhythmia.
- Women who have a positive pregnancy test at any time during the study period.
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
University of Cincinnati
Cincinnati, Ohio, 45267
Jenny Tong, MD, MPH, 513-558-4446, jenny.tong@uc.edu
Ahrar Haque, MD, 513-558-3923, haqueau@uc.edu
- Recruiting
Cincinnati Children's Hospital and Medical Center
Cincinnati, Ohio
Ahrar Haque, MD, 513-558-3923
About this study
To determine the role of nutrient status on ghrelin regulation of insulin secretion. We hypothesize that ghrelin and glucagon-like peptide-1 (GLP-1)(both are hormones made in the gut,) have differential effects on β-cell function in the fed state. We will compare insulin secretion and glucose turnover during meal ingestion using a dual glucose tracer and mixed meal protocol in subjects receiving ghrelin or saline. We will also determine the role of ghrelin-stimulated GLP-1 levels in this process using the GLP-1 receptor (GLP-1R) antagonist Exendin(9-39) (Ex-9).
Read the detailed description
We plan to study 20 healthy subjects on 4 occasions where they will receive ghrelin, ghrelin+Ex-9, Ex-9 or saline infusion after an overnight fast in a randomized order; Ex-9 will be used to block GLP-1 action. A 240-minute meal tolerance test (MTT) using a dual glucose tracer method will serve as the foundation of each study visit. One tracer, [6,6-2H2]glucose will be infused intravenously before and during the test meal to quantify fasting endogenous glucose production (EGP), and glucose disappearance during the meal. A second tracer, [U-13C]glucose, will be included in the meal to trace the appearance of oral glucose. The systemic appearance rates of both ingested tracer and total (i.e., ingested and endogenously produced) glucose will be calculated. Using this protocol, we will be able to evaluate a) insulin secretion in response to mixed-meal ingestion, b) glucose appearance and glucose disappearance during meal ingestion, c) the ghrelin effect on these parameters without GLP-1, and d) the effect of GLP-1 in the response based on the effects with and without Ex-9.
This dual-tracer method has been used to assess the ability of an individual to dispose of an oral glucose load, and accurately fractionates the appearance of ingested glucose in plasma (Ra meal), EGP, and peripheral glucose disposal (Rd) in this setting 41-42. The [6,6-2H2]glucose and [U-13C]glucose are stable-isotope tracers and are different from radioactive-isotope tracers in that they do not emit radiation.
All procedures will be performed at the CTRC at the Cincinnati Children's Hospital Medical Center (CCHMC).
- Conditions
- Diabetes
- Being tested
- Exendin (9-39), acyl ghrelin, saline
- Keywords
- ghrelin, glucose control, GLP-1, Exendin (9-39), insulin
- Medical subject headings
- Diabetes Mellitus, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exendin (9-39)Drug
acyl ghrelinDrug
salineDrug
| Study group | Role | What they receive |
|---|---|---|
| saline | Placebo comparator | Saline: 0.9% saline solution Receives: Drug: saline |
| ghrelin and exendin (9-39) | Experimental | Ghrelin+Ex-9: Combination of ghrelin and Ex-9, Receives: Drug: Exendin (9-39); Drug: acyl ghrelin |
| Exendin (9-39) | Experimental | Exendin (9-39) (25 µg/kg) bolus over 1 min followed by a continuous infusion of 2.5 µg/kg/min Receives: Drug: Exendin (9-39) |
| ghrelin | Experimental | synthetic human Acyl Ghrelin (0.28 μg/kg) bolus over 1 min followed by 2 μg/kg/h continuous infusion, Receives: Drug: acyl ghrelin |
What is being measured
The primary outcome is the main question the study is designed to answer.
post-prandial insulin secretion
Postprandial insulin secretion (ISR-meal) will be derived from plasma C-peptide concentrations during MTT using deconvolution with population estimates of C-peptide clearance.
Measured: 1 year
Secondary outcomes (11)
endogenous GLP-1 contribution to postprandial insulin secretion
The endogenous GLP-1 contribution to postprandial insulin secretion (GLP-1 effect) will be calculated as the difference in ISR-meal with and without Ex-9.
Measured: 1 year
β-cell response to glucose
An index of β-cell response to glucose will be calculated as the incremental insulin/glucose (I/G) AUC (ΔAUCI/G).
Measured: 1 year
insulin sensitivity
Whole body insulin sensitivity will be estimated using the Matsuda Index that has been well validated in large cohort studies and has demonstrated a good correlation with IVGTT or hyperinsulinemic-euglycemic clamp derived measures of insulin sensitivity. β-cell function (DI-meal) will be calculated as ΔAUCI/G x Matsuda Index
Measured: 1 year
fasting EGP
Fasting EGP will be calculated as the ratio of 6,6-[2H2]glucose infusion rate to plasma tracer enrichment (tracer-to-tracee ratio [TTR]6,6 from measurements obtained in the last 20 min of the basal tracer equilibration period, when plasma glucose concentration and 6,6-[2H2]glucose enrichment are stable).
Measured: 1 year
glucose appearance
Total rates of glucose appearance after meal ingestion (total Ra) will be calculated by modeling 6,6-[2H2] enrichment ([TTR]6,6) using both a two-compartment model and Steele's equation42. Meal glucose appearance will be determined from the analysis of [U-13C]-glucose fluxes. The meal will be labeled to 2.66% with U-13C]-glucose (TTRmeal). From the measurement of plasma [TTR]13C, we will calculate the exogenous (meal) glucose concentrations, [Gmeal] , from total glucose concentrations, [Gtot] , using the formula [Gmeal] = [Gtot] x [TTR]13C / TTRmeal as previously described 42,45. Endogenous glucose concentration [Gend] will be calculated as [Gend] = [Gtot] - [Gmeal].
Measured: 1 year
EGP during MTT
EGP during MTT will be calculated using model analysis of TTR of endogenous glucose ([TTR]end) and calculated as [TTR]end = [TTR]6,6 x [Gtot] / [Gend]
Measured: 1 year
exogenous glucose rate of appearance
Exogenous glucose rate of appearance, Ra meal, will be calculated by subtracting EGP during meal from total Ra (Ra meal = total Ra - EGP).
Measured: 1 year
metabolic glucose clearance
As for indexes of peripheral insulin sensitivity, we will calculate metabolic glucose clearance during MTT using peripheral glucose disposal (Rd) divided by glucose concentration (expressed as ml/min/kg) where Rd is calculated by subtracting the rate of change of plasma glucose mass from total Ra.
Measured: 1 year
area under the curve
AUC for glucagon, GLP-1, GIP, and free fatty acids (FFA), a measure of lipolysis.
Measured: 1 year
ghrelin measures
AG and total ghrelin levels will be measured during clamp-MTT.
Measured: 1 year
gastric emptying
Gastric emptying estimated by the gastric half-emptying time calculated from the emptying curve as the time when 50% of the total cumulated dose of acetaminophen has been eliminated46.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2012 (estimated)
- Study startApr 2013
- Primary completionApr 2014 (estimated)
- Study completionApr 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- David Dalessio
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor-investigator, David Dalessio, University of Cincinnati
- Investigators
- Jenny Tong, MD, MPH, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01729299
- Sponsor's protocol ID
- 12070904
- Status last verified
- Apr 2013
- First submitted
- 13 Nov 2012
- Last updated
- 4 Apr 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Page LC, Gastaldelli A, Gray SM, D'Alessio DA, Tong J. Interaction of GLP-1 and Ghrelin on Glucose Tolerance in Healthy Humans. Diabetes. 2018 Oct;67(10):1976-1985. doi: 10.2337/db18-0451. Epub 2018 Jul 31.
PubMed 30065032
Study at a glance
From the registry record, last updated by the sponsor on 4 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ghrelin Effect on Beta Cell Function in Health and Disease
- ClinicalTrials.gov ID
- NCT01729299
- Acronym / sponsor ID
- 12070904
- Conditions
- Diabetes
- Keywords
- ghrelin, glucose control, GLP-1, Exendin (9-39), insulin
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- David DalessioUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Apr 2013
- Primary completion
- Apr 2014 (estimated)
- Study completion
- Apr 2014 (estimated)
- First posted
- 20 Nov 2012 (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.
To determine the role of nutrient status on ghrelin regulation of insulin secretion. We hypothesize that ghrelin and glucagon-like peptide-1 (GLP-1)(both are hormones made in the gut,) have differential effects on β-cell function in the fed state. We will compare insulin secretion and glucose turnover during meal ingestion using a dual glucose tracer and mixed meal protocol in subjects receiving ghrelin or saline. We will also determine the role of ghrelin-stimulated GLP-1 levels in this process using the GLP-1 receptor (GLP-1R) antagonist Exendin(9-39) (Ex-9).
Detailed description
We plan to study 20 healthy subjects on 4 occasions where they will receive ghrelin, ghrelin+Ex-9, Ex-9 or saline infusion after an overnight fast in a randomized order; Ex-9 will be used to block GLP-1 action. A 240-minute meal tolerance test (MTT) using a dual glucose tracer method will serve as the foundation of each study visit. One tracer, [6,6-2H2]glucose will be infused intravenously before and during the test meal to quantify fasting endogenous glucose production (EGP), and glucose disappearance during the meal. A second tracer, [U-13C]glucose, will be included in the meal to trace the appearance of oral glucose. The systemic appearance rates of both ingested tracer and total (i.e., ingested and endogenously produced) glucose will be calculated. Using this protocol, we will be able to evaluate a) insulin secretion in response to mixed-meal ingestion, b) glucose appearance and glucose disappearance during meal ingestion, c) the ghrelin effect on these parameters without GLP-1, and d) the effect of GLP-1 in the response based on the effects with and without Ex-9.
This dual-tracer method has been used to assess the ability of an individual to dispose of an oral glucose load, and accurately fractionates the appearance of ingested glucose in plasma (Ra meal), EGP, and peripheral glucose disposal (Rd) in this setting 41-42. The [6,6-2H2]glucose and [U-13C]glucose are stable-isotope tracers and are different from radioactive-isotope tracers in that they do not emit radiation.
All procedures will be performed at the CTRC at the Cincinnati Children's Hospital Medical Center (CCHMC).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| saline | Placebo comparator | Drug: salineSaline: 0.9% saline solution |
| ghrelin and exendin (9-39) | Experimental | Drug: Exendin (9-39), Drug: acyl ghrelinGhrelin+Ex-9: Combination of ghrelin and Ex-9, |
| Exendin (9-39) | Experimental | Drug: Exendin (9-39)Exendin (9-39) (25 µg/kg) bolus over 1 min followed by a continuous infusion of 2.5 µg/kg/min |
| ghrelin | Experimental | Drug: acyl ghrelinsynthetic human Acyl Ghrelin (0.28 μg/kg) bolus over 1 min followed by 2 μg/kg/h continuous infusion, |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy men and women
- Ages between 18 and 45 years
- BMI between 18 and 29 kg/m2
Key exclusion criteria (7 listed)
- History or clinical evidence of impaired fasting glucose or diabetes mellitus, myocardial infarction within the past year, history or symptoms of congestive heart failure, uncontrolled hypertension, history or active liver or renal disease (AST or ALT >2x upper limits of normal, calculated glomerular filtration rate [GFR] <60).
- History of pituitary or adrenal disorders or neuroendocrine tumor.
- Anemia defined as hematocrit <33%.
- Use of medications that alter glucose metabolism
- Pregnancy or lactation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exendin (9-39) | Drug | Exendin (9-39), ghrelin and exendin (9-39) |
| acyl ghrelin | Drug | ghrelin, ghrelin and exendin (9-39) |
| saline | Drug | saline |
Primary outcome
post-prandial insulin secretion
Time frame: 1 year
Postprandial insulin secretion (ISR-meal) will be derived from plasma C-peptide concentrations during MTT using deconvolution with population estimates of C-peptide clearance.
11 secondary outcomes
endogenous GLP-1 contribution to postprandial insulin secretion
Time frame: 1 year
β-cell response to glucose
Time frame: 1 year
insulin sensitivity
Time frame: 1 year
fasting EGP
Time frame: 1 year
glucose appearance
Time frame: 1 year
EGP during MTT
Time frame: 1 year
exogenous glucose rate of appearance
Time frame: 1 year
metabolic glucose clearance
Time frame: 1 year
area under the curve
Time frame: 1 year
ghrelin measures
Time frame: 1 year
gastric emptying
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Apr 2013.
- Derived from this study: PubMed 30065032Page LC, Gastaldelli A, Gray SM, D'Alessio DA, Tong J. Interaction of GLP-1 and Ghrelin on Glucose Tolerance in Healthy Humans. Diabetes. 2018 Oct;67(10):1976-1985. doi: 10.2337/db18-0451. Epub 2018 Jul 31.
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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, MPH principal investigator
University of Cincinnati
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Exendin (9-39), acyl ghrelin and saline in people with Diabetes, run by David Dalessio at 2 sites 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 3 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 4 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jenny Tong, MD, MPH (513-558-4446, jenny.tong@uc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
post-prandial insulin secretion (time frame: 1 year). 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 NCT01729299, which also lists 1 linked publication.
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 4 Apr 2013.