- To study the response of active glucagon-like peptide-1 (GLP1), Glucagon, Insulin, C-peptide and growth hormone (GH) and liver gluconeogenesis to a glucagon challenge in healthy volunteers- To study the expression of glucagon receptor mRNA in the…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Serum concentrations of (labelled)glucose, glucagon, insulin, C-peptide, GH and
active GLP1, glucose levels with a continuous glucose monitoring device,
calculation of hepatic glucose production and expression of glucagon receptor
mRNA.
Secondary outcome
Tolerability of biopsies, glucose monitoring and glucagon challenge
Background summary
A hyperglucagonemic hyperglycemic test or glucagon challenge has been performed
to assess hepatic glucose production. The challenge can be used as a tool to
assess the anti-glucagonaemic effect of a pharmacological or dietary
intervention. Another validated tool to assess these effects is to measure cell
surface glucagon receptor density or glucagon receptor mRNA levels in
subcutaneous fat cells.
However, the glucagon challenge has been described only once in literature and
experience needs to be build. Moreover, fat biopsies have been predominantly
performed in abdominal tissue and direct comparison with other sites is
missing. This is potentially problematic as abdominal subcutaneous
administration of drugs is commonly used and assessment of drug effects in
abdominal subcutaneous fat tissue may yield erroneous results. This may be
circumvented by using alternative locations to obtain fat tissue, i.e. biopsies
from the dorsal gluteal area.
In addition, continuous glucose monitoring has become available for application
in diabetes patients. However, this remains an unvalidated tool in healthy
volunteers
Study objective
- To study the response of active glucagon-like peptide-1 (GLP1), Glucagon,
Insulin, C-peptide and growth hormone (GH) and liver gluconeogenesis to a
glucagon challenge in healthy volunteers
- To study the expression of glucagon receptor mRNA in the abdominal and dorsal
fat cell.
- To assess the quality of continuous glucose monitoring in comparison with
plasma and capillary blood glucose determination in healthy volunteers
- To assess tolerability of abdominal and dorsal fat biopsies, a glucagon
challenge and continuous glucose monitoring
Study design
Non-randomized, prospective, intervention and response study
Study burden and risks
In this short study of approximately 26 hours measurements are spread over the
occassion. The fat biopsies are performed on the evening before the glucagon
challange.
Especially during the glucagon challange the number of measurements is
extensive. Subjects will be asked to stay in bed for five hours.
The glucagon challenge has been performed before. In this previous study a
longer challange was used (with similar doasage regimes) and no adverse events
occured. We expect no problems with regard to the burden fand risk of
participation.
Zernikedreef 10
2333 CL Leiden
Nederland
Zernikedreef 10
2333 CL Leiden
Nederland
Listed location countries
Age
Inclusion criteria
- Able and willing to provide written informed consent
- Age 18 to 65 years
- Males or females
Exclusion criteria
- Clinically significant abnormalities in medical history, physical examination or
laboratory examination
- Pregnanant or breast feeding females
- Not able or willing to use an acceptable contraceptive method for study duration
for females (hormonal contraceptives, intra-uterine device or condom/pessary)
- Not able and willing to refrain from smoking and/or xanthine use on study day
- Fasting plasma glucose at screening >= 6.4
- HbA1C >= 7%
- BMI >= 30 kg/m2
- Hypertension (systolic blood pressure >= 140 mm Hg or a diastolic blood pressure >=
95 mm Hg)
- Suspicion of a pheochromocytoma (i.e. Rapid heart rate, palpitations, excessive
sweating, chest pain, upper abdominal pain, severe headaches, tremors, feeling
of anxiety or extreme fright, pale skin)
- Positive urine testing for cocaine, opiates (morphine) and/or THC at screening
- Use of concomitant medication (except hormonal contraceptives)
- Positive test result for HIV, hepatitis B virus, and/or hepatitis C virus
- History of alcohol or drug abuse
- Undergoing or have undergone treatment with another investigational drug,
biologic agent or device within 90 days prior to Screening.
- Blood donation within three months of screening
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2007-002215-30-NL |
| Other | na |
| CCMO | NL17672.058.07 |