Trial · Interventional

TerminatedPhase 1Results postedRegistry data

Pharmacogenomics of GLP1 Receptor Agonists

NCTNCT05762744Other idHP-00067574

Open at ClinicalTrials.govAsk about this trial

This trial was stopped early.

Reason given at the registry: We concluded that it would not be possible to meet our recruitment targets within the available budget. The study was ended when the funding ended.

Results were posted for this trial.

Overview

Status: Terminated
Phase: Phase 1
Enrollment: 63 participants (actual)
Sponsor: University of Maryland, Baltimore · Other
Design: Randomized · Single masking
Countries: 1 country
United States
Start: 1 Jun 2016
Primary completion: 30 Nov 2018
Completion: 31 Oct 2022
First posted: 10 Mar 2023
Last update posted: 1 Jul 2025
Conditions: Type 2 Diabetes

Timeline

1 trial · 1 stopped early · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2016201820202022

Ph 1
Pharmacogenomics of GLP1 Receptor Agonists
NCT05762744
1 Jun 2016 to 31 Oct 2022
Terminated
Terminated

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Healthy volunteers were recruited from the Old Order Amish population in Lancaster County, Pennsylvania. After providing informed consent, research participants were screened for eligibility. The clinical trial was designed as a randomized crossover study in which participants underwent two frequently sampled intravenous glucose tolerance tests - one after receiving a subcutaneous injection of saline and one after receiving a subcutaneous injection of rapid-acting exenatide (BYETTA). The study sought to determine whether genetic variants are associated with the magnitude of the effect of exenatide. However, because the study fell far short of its recruitment targets, it was under-powered to evaluate genetic association. Thus, the data analysis focused on testing the hypothesis that the order of testing (whether the placebo FSIGT was conducted before the exenatide-stimulated FSIGT or whether the FSIGTs were conducted in the reverse order) does not alter the magnitude impact of exenatide on responses to a frequently sampled iv glucose tolerance test.

Interventions

Exenatide Injection (before the first FSIGT)Drug
Exenatide injection before the second FSIGT)Drug

Arms2

Other
Exenatide followed by saline
Participants were randomized to receive exenatide 15 min before the first frequently sampled iv glucose tolerance test and saline 15 min before the second frequently sampled iv glucose tolerance test
Other
Saline followed by exenatide
Participants were randomized to receive saline15 min before the first frequently sampled iv glucose tolerance test and exenatide15 min before the second frequently sampled iv glucose tolerance test

Primary outcomes2

Outcomes the sponsor listed as primary.

Exenatide Effect on First Phase Insulin Secretion
Time frame · 0-10 minutes
Registry description
The ratio of the area-under-the-curve (AUC) for 1st phase insulin secretion in the exenatide-stimulated FSIGT divided by the AUC for 1st phase insulin secretion in the saline FSIGT.
Exenatide Effect on Glucose Disappearance Rate
Time frame · 25-50 minutes
Registry description
The ratio of the glucose disappearance rate (exenatide) divided by the glucose disappearance rate (placebo). Glucose disappearance rates were calculated as the slope of the plot of the logarithm of the glucose concentration as a function of time.

Secondary outcomes(6)

Glucose Disappearance Rate (Exenatide)
Time frame · 25-50 minutes
Registry description
The slope of the line plotting the logarithm of glucose concentrations as a function of time during the exenatide frequently sampled intravenous glucose tolerance test. The slope of the line was estimated as the slope of the least-squares fit to the data points between 25-50 minutes.
Glucose Disappearance Rate (Placebo)
Time frame · 25-50 minutes
Registry description
The slope of the line plotting the logarithm of glucose concentrations as a function of time during the placebo frequently sampled intravenous glucose tolerance test. The slope of the line was estimated as the slope of the least-squares fit to the data points between 25-50 minutes.
First Phase Insulin Secretion (Exenatide)
Time frame · 0-10 minutes
Registry description
The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received exenatide
First Phase Insulin Secretion (Placebo)
Time frame · 0-10 minutes
Registry description
The area under the curve for plasma insulin levels during a frequently sampled intravenous glucose tolerance test after participants received saline
Drug Effect on First-Phase Insulin Secretion (Genotype-specific)
Time frame · 0 - 10 min during the FSIGT
Registry description
The effect of exenatide to increase first-phase insulin secretion was defined as the ratio of area-under-the-curve (AUC) for insulin levels during the first 10 minutes of the exenatide-stimulated FSIGT divided by the AUC for first phase insulin secretion during the saline FSIGT..
Exenatide's Effect on the Rate of Glucose-disappearance (Genotype Specific)
Time frame · 25-50 min during the FSIGT
Registry description
The rate of glucose disappearance was calculated as the slope of a least-squared line fitted to the logarithms of glucose concentrations during time 25-50 min of FSIGTs

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· 0-10 minutes

Exenatide Effect on First Phase Insulin Secretion

Group	Value (Ratio (no units))	Spread
Exenatide First Followed by Saline	1.90	0.17
Saline First Followed by Exenatide	2.18	0.25

Primary outcomeMean· 25-50 minutes

Exenatide Effect on Glucose Disappearance Rate

Group	Value (Ratio (no units))	Spread
Exenatide First Followed by Saline	2.16	0.19
Saline First Followed by Exenatide	2.28	0.20

Secondary and other outcome results(6)

Secondary outcomeMean· 25-50 minutes

Glucose Disappearance Rate (Exenatide)

Group	Value (Log(mg/dL) per min)	Spread
Exenatide First Followed by Saline	1056	94
Saline First Followed by Exenatide	1131	81

Secondary outcomeMean· 25-50 minutes

Glucose Disappearance Rate (Placebo)

Group	Value (Log(mg/dL) per min)	Spread
Exenatide First Followed by Saline	500	37
Saline First Followed by Exenatide	547	48

Secondary outcomeMean· 0-10 minutes

First Phase Insulin Secretion (Exenatide)

Group	Value (microunits/mL*min)	Spread
Exenatide First Followed by Saline	561	94
Saline Followed by Exenatide	494	50

Secondary outcomeMean· 0-10 minutes

First Phase Insulin Secretion (Placebo)

Group	Value (microunits/mL*min)	Spread
Exenatide First Followed by Normal Saline	305	38
Placebo First Followed by Exenatide	254	23

Secondary outcomeMean· 0 - 10 min during the FSIGT

Drug Effect on First-Phase Insulin Secretion (Genotype-specific)

Group	Value (Ratio: no units)	Spread
Major Allele Homozygotes	2.25	0.31
Homozygotes for the p.G40S Allele of GCGR	1.94	0.21
Homozygotes for the p.E354Q Allele of GIPR	1.87	0.27

Secondary outcomeMean· 25-50 min during the FSIGT

Exenatide's Effect on the Rate of Glucose-disappearance (Genotype Specific)

Group	Value (Log(mg/dL) per min)	Spread
Major Allele Homozygotes	2.19	0.24
Homozygotes for the p.G40S Allele of GCGR	2.28	0.24
Homozygotes for the p.E354Q Allele of GIPR	2.18	0.19

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Total Study Population (Control Study)The analysis is based on observations during the control studies in the 62 individuals who completed the control intravenous glucose tolerance testing. We report the adverse events separately for the control studies versus the exenatide studies because the literature documents the fact that GLP1R agonists like exenatide frequently induce nausea and/or vomiting.	0 / 62	0 / 62	3 / 62
Total Study Population (Exenatide Study)The analysis is based on observations during the control studies in the 62 individuals who completed exenatide intravenous glucose tolerance testing. We report the adverse events separately for the control studies versus the exenatide studies because the literature documents the fact that GLP1R agonists like exenatide frequently induce nausea and/or vomiting.	0 / 62	0 / 62	7 / 62

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

More studies

1 study on this page

PubMed tag: none · 2023

Acute pharmacodynamic responses to exenatide: Drug-induced increases in insulin secretion and glucose effectiveness.

Taylor et al. 2023Diabetes, obesity & metabolismcited by 5

PMID 37264484PMC10524849DOI 10.1111/dom.15143PUB-37264484

Rights unknown

Source link

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

DerivedBeitelshees AL, Streeten EA, Shahidzadeh Yazdi Z, Whitlatch HB, Mitchell BD, Shuldiner AR, Montasser ME, Taylor SI. Acute pharmacodynamic responses to sitagliptin: Drug-induced increase in early insulin secretion in oral glucose tolerance test. Clin Transl Sci. 2024 May;17(5):e13809. doi: 10.1111/cts.13809. PMID 38700326

Eligibility

Who could join, as posted.

Sex: All
Age: from 18 Years
Healthy volunteers: Accepted

Inclusion and exclusion criteria, as posted

Inclusion Criteria: * Member of the Old Order Amish community in Lancaster County, Pennsylvania * BMI: 18-40 kg/sq.m. Exclusion Criteria: * Known allergy to exenatide * History of diabetes, random glucose \>200 mg/dL, or HbA1c \> 6.5% * Significant debilitating chronic cardiac, hepatic, pulmonary, or renal disease or other diseases that the investigator judges will make interpretation of the results difficult or increase the risk of participation * Seizure disorder * Pregnant by self-report or known pregnancy within 3 months of the start of study * Currently breast feeding or breast feeding within 3 months of the start of the study * Estimated glomerular filtration rate \<60 mL/min/1.73m2 * Hematocrit \<35% * Liver function tests greater than 2 times the upper limit of normal * Abnormal thyroid stimulating hormone * History of pancreatitis or pancreatic cancer. Personal or family history of medullary carcinoma of the thyroid.

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