Insulin SensitivityEarly Phase 1GlucagonNCT04300049
Effect of Physiologic Hyperglucogonemia on Adipocyte Metabolism
A Early Phase 1 study testing Glucagon Infusion and Saline in people with Insulin Sensitivity, run by The University of Texas Health Science Center at San Antonio at 2 sites in United States.
Trial summary
Purpose/Objectives: To investigate the effect of hyperglucagonemia on insulin action, particularly on adipose tissue. Research Design/Plan: Normal glucose tolerant subjects will be studied. Study subjects will receive a continuous glucagon infusion for 12 hours. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Insulin Sensitivity
- What is being tested?
- Glucagon Infusion and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 Feb 2018to 15 Nov 2023
- Phase
- Early 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Fasting Glucose < 100 mg/dl
- HbA1C < 5.7%
- 2-h OGTT value < 140 mg/dl
- Good general Health as determined by medical history, physical exam, screening lab tests, urinalysis, and EKG.
- Weight Stable (±3 lbs) over the preceding 3 months
- ages from 18-50
- Male/Female
- BMI from 23-28 kg/m2 -
Who cannot join
- Subjects who participate in an excessively heavy exercise program.
- Subjects taking any medication known to affect glucose tolerance will be excluded.
- Cannot be pregnant
- Hyper sensitive to glucagon
- -
Trial locations and contacts
2 sites in 1 country.
United States2 sites
South Texas Veterans Health Care Center
San Antonio, Texas, 78229
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
Purpose/Objectives: To investigate the effect of hyperglucagonemia on insulin action, particularly on adipose tissue.
Research Design/Plan: Normal glucose tolerant subjects will be studied. Study subjects will receive a continuous glucagon infusion for 12 hours. Following glucagon infusion, subjects will receive prime-continuous tracer infusions for additional 4 hours to measure adipocyte metabolism. Within 6-8 weeks, subjects will return for a repeat study with normal saline as a control group.
Read more
Methods: All subjects will have an oral glucose tolerance test prior to participation to confirm they are normal glucose tolerant. Subjects will be admitted to the CRC at 4 PM and will receive a continuous glucagon for 12 hours. At 6 AM on the following morning, subjects will receive prime-continuous tracer infusions of the following for 4 hours (14C-glycerol, 3-3H glucose, and D2O). At 10 AM continuous indirect calorimetry will be performed to determine rates of energy expenditure and glucose/lipid oxidation for 40 minutes. At 6 AM a surgical biopsy of abdominal adipose tissue will be performed for measurement of adipocyte metabolism. At 8 AM, the study team will infuse insulin/glucose to test for insulin sensitivity.
Clinical Relevance: The results of this study will help the study team to further understand the pathophysiology of metabolic disturbances that is induced by hyperglucagonemia in type 2 diabetes patients.
Read the detailed description
Visit 1 Screening: All subjects will be performed indirect calorimetry to determine rates of energy expenditure and glucose/lipid oxidation for 40 minutes prior to all other procedures to obtain a fasting calorimetry. Subjects then will have a 75 gram oral glucose tolerance test to document the presence of normal glucose tolerance. Blood will be drawn at -30, -15, 0 and at 15, 30, 45, 60, 90 and 120 minutes thereafter for the determination of plasma glucose, insulin, C-peptide, glucagon, FFA, glycerol, GLP-1 and GIP concentrations. The total amount of blood to be taken during the OGTT is 148 ml or about 10 tablespoons. Participants will also undergo a total body fat (DXA) and hepatic fat content (MRS). Subjects will also have a routine physical exam, an ECG, weight, height, vitals and collection of prior medical history. The study team will also check blood glucose (sugar) and blood lipid (fat) levels. The total amount of blood that we will take for the screening blood tests, HbA1c, lipid, and other blood tests is 34 ml or about 2 1/3 tablespoons.
Visit 2 Adipose Tissue Metabolism Measurement: Subjects (n=12) will be admitted to the CRC at 4 PM on the day prior to study and received a standardized, weight maintaining diet containing 50% CHO: 30% fat: 20% protein. At 6 PM subjects will receive a continuous glucagon (3 ng/kg.min, N=6) or glucagon (6 ng/kg.min, N=6) for 12 hours. Subjects will remain fasting after 10 PM. Samples for glucagon, FFA, insulin and C-peptide will be collected at 1700, 1730, 1800, 1900, 2100, 2300, 0100, 0300, and 0500 hours.
At 6 AM on the following morning subjects will receive prime-continuous tracer infusions of the following for 4 hours (see figure 1):
(i) 14-C-glycerol (prime = 30 µCi; continuous infusion = 0.3 µCi/min) for determination of total body rate of lipolysis.
(ii) 3-3H-glucose (prime = 40 µCi; continuous infusion = 0.4 µCi/min) for determination of rates of total body glucose appearance and disappearance.
(iii) D2O (5 g/kg fat free mass at 9 PM orally) to determine the rate of de novo lipogenesis.
At 6 AM a surgical biopsy of subcutaneous abdominal adipose tissue will be performed for measurement of hormone sensitive (HSL) lipase activity, AMPK activity, and serine phosphorylation of HSL (see Figure 2), FGF-21, FAP, Beta-klotho. Insulin signaling (IR/IRS-1 tyrosine phosphorylation, PI-3 kinase activity, Akt) molecules, GLUT4, markers of inflammation (IkB, NF-kB, T4R4TLR4, JNK, p38 MAPK, M2/M1 macrophages, IL-1, IL-6, TNF alpha, MCP-1) also will be measured on the fat biopsy. Lipidomic analysis to quantitate the amount of and type of fat in the adipose tissue biopsy also will be performed. After surgical biopsy of adipose tissue, starting the tracer equilibration (6AM) blood will be drawn every 15-30 minutes for 4 hours (6-10 AM) for substrate (glucose, FFA, glycerol, triglycerides), hormone (glucagon, insulin, C-peptide, GLP-1, GIP, adiponectin, leptin, FGF21 [active and total], FAP [degrading enzyme]), radioisotope (14-C-glycerol and 3-3H glucose) specific activity. Participants will place their hand in a transparent plastic thermo-regulated box heated to 50-60°C (122-140°F) to ensure good blood flow to the hand. Pasma samples for radioisotope activity (background) will be obtained at 6 AM. At 9 AM continuous indirect calorimetry will be performed to determine rates of energy expenditure and glucose/lipid oxidation for 40 minutes.
The glucagon infusion will be continued through the 4-hour tracer infusion (i.e. 6AM-10AM). At the end of the glucagon infusion (~10 AM) a repeat measurement of hepatic fat content will be obtained. A total of 366 ml of blood will be drawn.
At 8 AM the insulin sensitivity test will be done during the last two hours of the tracer infusion. During the 2 hours of the insulin sensitivity test, the insulin (60 mU/m2 ⋅ min) and glucose will be given through the catheter in the vein in the subject's arm to determine rates of whole-body insulin sensitivity. There are no expect adverse reactions to be experienced by the subjects during both infusions.
- Conditions
- Insulin Sensitivity
- Being tested
- Glucagon Infusion, Saline
- Keywords
- glucagon, Lipolysis
- Medical subject headings
- Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Glucagon InfusionDrug
Also called IV Glucagon
Study participants will receive glucagon infusion (6ug/kg/min for 12 hours) 12 hours.
SalineOther
Also called Normal saline
Study participants will receive saline infusion for 12 hours.
| Study group | Role | What they receive |
|---|---|---|
| Change in Glycerol Ra | Experimental | The difference in rate of lipolysis (glycerol Ra) during the basal state (-120 -0 minute) between subjects receiving glucagon and saline represents the change in whole body lipolysis caused by glucagon. Receives: Drug: Glucagon Infusion; Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
the rate of glycerol turnover
effect of glucagon infusion on whole body lipolysis,
Measured: 12 hours after the infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2020
- Study start5 Feb 2018
- Primary completion15 Nov 2023
- Study completion15 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Insulin SensitivityStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- single arm before and after glucagon vs. saline
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- South Texas Veterans Health Care System
- Responsible party
- Sponsor
- Investigators
- Ralph DeFronzo, MD, Principal investigator, University of Texas Health San Antonio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04300049
- Sponsor's protocol ID
- HSC20170682H
- Acronym
- Glucagon
- Status last verified
- Oct 2024
- First submitted
- 5 Mar 2020
- Last updated
- 21 Oct 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Physiologic Hyperglucogonemia on Adipocyte Metabolism
- ClinicalTrials.gov ID
- NCT04300049
- Acronym / sponsor ID
- Glucagon / HSC20170682H
- Conditions
- Insulin Sensitivity
- Keywords
- glucagon, Lipolysis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- South Texas Veterans Health Care System
- Study start
- 5 Feb 2018 (actual)
- Primary completion
- 15 Nov 2023 (actual)
- Study completion
- 15 Nov 2023 (actual)
- First posted
- 9 Mar 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.
Purpose/Objectives: To investigate the effect of hyperglucagonemia on insulin action, particularly on adipose tissue.
Research Design/Plan: Normal glucose tolerant subjects will be studied. Study subjects will receive a continuous glucagon infusion for 12 hours. Following glucagon infusion, subjects will receive prime-continuous tracer infusions for additional 4 hours to measure adipocyte metabolism. Within 6-8 weeks, subjects will return for a repeat study with normal saline as a control group.
Methods: All subjects will have an oral glucose tolerance test prior to participation to confirm they are normal glucose tolerant. Subjects will be admitted to the CRC at 4 PM and will receive a continuous glucagon for 12 hours. At 6 AM on the following morning, subjects will receive prime-continuous tracer infusions of the following for 4 hours (14C-glycerol, 3-3H glucose, and D2O). At 10 AM continuous indirect calorimetry will be performed to determine rates of energy expenditure and glucose/lipid oxidation for 40 minutes. At 6 AM a surgical biopsy of abdominal adipose tissue will be performed for measurement of adipocyte metabolism. At 8 AM, the study team will infuse insulin/glucose to test for insulin sensitivity.
Clinical Relevance: The results of this study will help the study team to further understand the pathophysiology of metabolic disturbances that is induced by hyperglucagonemia in type 2 diabetes patients.
Detailed description
Visit 1 Screening: All subjects will be performed indirect calorimetry to determine rates of energy expenditure and glucose/lipid oxidation for 40 minutes prior to all other procedures to obtain a fasting calorimetry. Subjects then will have a 75 gram oral glucose tolerance test to document the presence of normal glucose tolerance. Blood will be drawn at -30, -15, 0 and at 15, 30, 45, 60, 90 and 120 minutes thereafter for the determination of plasma glucose, insulin, C-peptide, glucagon, FFA, glycerol, GLP-1 and GIP concentrations. The total amount of blood to be taken during the OGTT is 148 ml or about 10 tablespoons. Participants will also undergo a total body fat (DXA) and hepatic fat content (MRS). Subjects will also have a routine physical exam, an ECG, weight, height, vitals and collection of prior medical history. The study team will also check blood glucose (sugar) and blood lipid (fat) levels. The total amount of blood that we will take for the screening blood tests, HbA1c, lipid, and other blood tests is 34 ml or about 2 1/3 tablespoons.
Visit 2 Adipose Tissue Metabolism Measurement: Subjects (n=12) will be admitted to the CRC at 4 PM on the day prior to study and received a standardized, weight maintaining diet containing 50% CHO: 30% fat: 20% protein. At 6 PM subjects will receive a continuous glucagon (3 ng/kg.min, N=6) or glucagon (6 ng/kg.min, N=6) for 12 hours. Subjects will remain fasting after 10 PM. Samples for glucagon, FFA, insulin and C-peptide will be collected at 1700, 1730, 1800, 1900, 2100, 2300, 0100, 0300, and 0500 hours.
At 6 AM on the following morning subjects will receive prime-continuous tracer infusions of the following for 4 hours (see figure 1):
(i) 14-C-glycerol (prime = 30 µCi; continuous infusion = 0.3 µCi/min) for determination of total body rate of lipolysis.
(ii) 3-3H-glucose (prime = 40 µCi; continuous infusion = 0.4 µCi/min) for determination of rates of total body glucose appearance and disappearance.
(iii) D2O (5 g/kg fat free mass at 9 PM orally) to determine the rate of de novo lipogenesis.
At 6 AM a surgical biopsy of subcutaneous abdominal adipose tissue will be performed for measurement of hormone sensitive (HSL) lipase activity, AMPK activity, and serine phosphorylation of HSL (see Figure 2), FGF-21, FAP, Beta-klotho. Insulin signaling (IR/IRS-1 tyrosine phosphorylation, PI-3 kinase activity, Akt) molecules, GLUT4, markers of inflammation (IkB, NF-kB, T4R4TLR4, JNK, p38 MAPK, M2/M1 macrophages, IL-1, IL-6, TNF alpha, MCP-1) also will be measured on the fat biopsy. Lipidomic analysis to quantitate the amount of and type of fat in the adipose tissue biopsy also will be performed. After surgical biopsy of adipose tissue, starting the tracer equilibration (6AM) blood will be drawn every 15-30 minutes for 4 hours (6-10 AM) for substrate (glucose, FFA, glycerol, triglycerides), hormone (glucagon, insulin, C-peptide, GLP-1, GIP, adiponectin, leptin, FGF21 [active and total], FAP [degrading enzyme]), radioisotope (14-C-glycerol and 3-3H glucose) specific activity. Participants will place their hand in a transparent plastic thermo-regulated box heated to 50-60°C (122-140°F) to ensure good blood flow to the hand. Pasma samples for radioisotope activity (background) will be obtained at 6 AM. At 9 AM continuous indirect calorimetry will be performed to determine rates of energy expenditure and glucose/lipid oxidation for 40 minutes.
The glucagon infusion will be continued through the 4-hour tracer infusion (i.e. 6AM-10AM). At the end of the glucagon infusion (~10 AM) a repeat measurement of hepatic fat content will be obtained. A total of 366 ml of blood will be drawn.
At 8 AM the insulin sensitivity test will be done during the last two hours of the tracer infusion. During the 2 hours of the insulin sensitivity test, the insulin (60 mU/m2 ⋅ min) and glucose will be given through the catheter in the vein in the subject's arm to determine rates of whole-body insulin sensitivity. There are no expect adverse reactions to be experienced by the subjects during both infusions.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- single arm before and after glucagon vs. saline
| Arm | Type | Receives |
|---|---|---|
| Change in Glycerol Ra | Experimental | Drug: Glucagon Infusion, Other: SalineThe difference in rate of lipolysis (glycerol Ra) during the basal state (-120 -0 minute) between subjects receiving glucagon and saline represents the change in whole body lipolysis caused by glucagon. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Fasting Glucose < 100 mg/dl
- HbA1C < 5.7%
- 2-h OGTT value < 140 mg/dl
- Good general Health as determined by medical history, physical exam, screening lab tests, urinalysis, and EKG.
- Weight Stable (±3 lbs) over the preceding 3 months
Key exclusion criteria (5 listed)
- Subjects who participate in an excessively heavy exercise program.
- Subjects taking any medication known to affect glucose tolerance will be excluded.
- Cannot be pregnant
- Hyper sensitive to glucagon
- -
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 |
|---|---|---|
| Glucagon InfusionAlso: IV GlucagonStudy participants will receive glucagon infusion (6ug/kg/min for 12 hours) 12 hours. | Drug | Change in Glycerol Ra |
| SalineAlso: Normal salineStudy participants will receive saline infusion for 12 hours. | Other | Change in Glycerol Ra |
Primary outcome
the rate of glycerol turnover
Time frame: 12 hours after the infusion
effect of glucagon infusion on whole body lipolysis,
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 21 Oct 2024.
- 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.
Ralph DeFronzo, MD principal investigator
University of Texas Health San Antonio
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Glucagon Infusion and Saline in people with Insulin Sensitivity, run by The University of Texas Health Science Center at San Antonio 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 8 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 21 Oct 2024. 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. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
the rate of glycerol turnover (time frame: 12 hours after the infusion). 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 21 Oct 2024.