Chronic Nausea and Vomiting Syndrome, Functional Dyspepsia, Gastroparesis, Healthy
Conditions
Keywords
Liraglutide, GLP-1 Receptor Agonist, Gastric Motility, Body Surface Gastric Mapping, Gastric Emptying Breath Test
Brief summary
Aim 1: To investigate, in healthy participants, the effect of liraglutide injection on gastric electrophysiology (as measured by body surface gastric mapping using the Gastric Alimetry device) during an 13-dayramping dose of liraglutide and subsequent washout. Aim 2: Assessment of effect of liraglutide injection on gastrointestinal symptoms and gut-brain wellbeing (as measured by validated symptom App and Alimetry gut-brain wellness Scale, respectively) during an 13-day ramping dose of liraglutide and subsequent washout.
Detailed description
Globally, more than 40% of persons have a functional gastrointestinal(GI) disorder based on the Rome IV diagnostic questionnaire. These disorders encompass gastroparesis and chronic nausea and vomiting syndromes (CNVS; including chronic unexplained nausea and vomiting(CNV) and cyclic vomiting syndrome (CVS)), functional dyspepsia (FD; chronic indigestion), and post-operative gastric dysfunction. The disorders are linked by the fact that no obvious structural cause for their symptoms can be identified, based on investigations such as endoscopy or imaging. However, there is still a lack of diagnostic biomarkers for these functional disorders. Measuring gastric emptying rate with either scintigraphy or a breath test is the only clinically used test of gastric function; if abnormal the patient is listed as having gastroparesis. However, this test fails to clearly explain the symptom pattern and severity, does not predict response to therapy and changes in the test result do not correlate with evolution of clinical symptoms. There is also substantial crossover in symptoms between functional dyspepsia and gastro-esophageal reflux disease, and differentiating these condition scan be challenging. GLP-1 analogues cause GI distress and weight loss due to their effect on slowing gastric emptying, inducing satiety or loss of appetite, and thus reducing oral intake. GI symptoms such as nausea, similar to symptoms of gastroparesis, are the most common reason for discontinuation of these drugs. Gastric Alimetry (GA) is a new device which measures gastric electrophysiology. We postulate that GA will show changes in gastric spectral analysis as well as symptoms in healthy volunteers on a once daily injectable GLP-1 analogue, liraglutide. References: Sperber AD, Bangdiwala SI, Drossman DA, Ghoshal UC, Simren M, TackJ, Whitehead WE, Dumitrascu DL, Fang X, Fukudo S, Kellow J.Worldwide prevalence and burden of functional gastrointestinaldisorders, results of Rome Foundation Global Study. Gastroenterology. 2021;160(1):99-114 Pasricha PJ, Grover M, Yates KP,Abell TL, Bernard CE, Koch KL, McCallum RW, Sarosiek I, Kuo B, BulatR, Chen J. Functional dyspepsia and gastroparesis in tertiary care areinterchangeable syndromes with common clinical and pathologicfeatures. Gastroenterology. 2021;160(6):2006-17 Parkman, Henry P.,Daniel S. Rim, Jonathan R. Anolik, Simin Dadparvar, and Alan H. Maurer.2024. "Glucagonlike Peptide-1 Receptor Agonists: The Good, the Bad,and the Ugly-Benefits for Glucose Control and Weight Loss with SideEffects of Delaying Gastric Emptying." Journal of Nuclear MedicineTechnology, January. https://doi.org/10.2967/jnmt.123.266800.
Interventions
All study participants will be in this group and will have a total of three body surface gastric mapping tests conducted, pre, during and post liraglutide.
Sponsors
Alimetry
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
This is a Open-label, single site, prospective, proof of concept evaluation of the effect of liraglutide, a NZ-approved daily injectableGLP-1 agonist, on Gastric Alimetry (GA) outputs in up to 20 healthy volunteers. GA will be performed at baseline, after a 12-14 day ascending dose of liraglutide, and after a minimum 5 day washout period. This approach directly compares GA within subjects with a gastric-focused pharmacological intervention compared to baseline and after a washout phase. The primary endpoint is a change in GA-RI which isa metric used to define gastric dysrhythmia which is seen in disease states such as neuromuscular disorders and gastroparesis. Since there is no reference standard for GA to compare to, this study will instead allow fulfilment of key plausibility criteria for measuring GA in disease (i.e. inducing symptoms and GA changes in healthy subjects with no previous symptoms.) It will also show that the effects are reversible after stopping the medication.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Provision of signed and dated informed consent form, AND * Aged between 18 and 65 years old, AND * Healthy volunteer with no previous history of gastrointestinal disorders/symptoms * BMI 22-35
Exclusion criteria
1. Confirmed diagnosis of a comorbidity known to affect gastric motility (i.e., Parkinson's Disease, Type 1 or 2 Diabetes). 2. Medications in the last 3 months known to impact gastric motility. 3. Any Gastric Surgery 4. Pregnancy or lactation, determined by pregnancy test at timeof enrolment. 5. Known allergy to adhesives and/or skin sensitivities, or any allergy to liraglutide or any components of the liraglutide/Saxenda formulation, or known hypersensitivity to Spirulina, egg, milk or wheat allergens 6. Use of GLP-1 agonist and/or on regular insulin in the past 3months. 7. History of gastroduodenal dysfunction and/or meets the ROME IV symptom criteria for a gastroduodenal disorder of gut-brain interaction (functional dyspepsia, chronic nausea and vomiting syndrome, cyclic vomiting syndrome, rumination syndrome, cannabinoid hyperemesis syndrome, or a belching disorder). 8. History of peptic ulcer, pancreatitis, cholelithiasis, choledocholithiasis, History of kidney or hepatic dysfunction 9. History of psychiatric disturbance requiring medication in the year before enrolment, any history of suicide attempt or eating disorder 10. History of Type II Diabetes or glucose intolerance (treated or untreated) 11. History of cancer other than basal cell skin cancer, and patients with personal or family history of medullary thyroid carcinoma (MTC) or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2) 12. History of angioedema or urticaria disorder 13. History of cardiac disorder or arrhythmia 14. Any tobacco, vaping or cannabinoid use in the 30 days prior to study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in overall postprandial BSGM Gastric Alimetry Rhythm Index (GA-RI) on treatment compared to baseline. | 2 weeks | Change in overall postprandial BSGM Gastric Alimetry Rhythm Index (GA-RI) on treatment compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in overall postprandial BMI-adjusted amplitude on treatment compared to baseline | 2 weeks | Change in overall postprandial BMI-adjusted amplitude on treatment compared to baseline |
| Change in GA-RI on treatment to washout | 1 week | Change in GA-RI on treatment to washout |
| Change in BMI-adjusted amplitude on treatment to washout | 1 week | Change in BMI-adjusted amplitude on treatment to washout |
| Correlation of total symptom burden with change in GA-RI | 4 weeks | Correlation of total symptom burden with change in GA-RI |
| Change in the following symptoms on treatment compared to baseline | 2 weeks | GCSI-DD (3 day average, last 3 days on treatment vs 3 days baseline) Alimetry total symptom burden Alimetry individual symptoms |
| Change in gastric emptying half-time on treatment compared to baseline | 2 weeks | Change in gastric emptying half-time on treatment compared to baseline |
| Correlation of gastric emptying half-time with GA-RI on treatment | 2 weeks | Correlation of gastric emptying half-time with GA-RI on treatment |
| Correlation of gastric emptying half-time with total symptom burden on treatment | 2 weeks | Correlation of gastric emptying half-time with total symptom burden on treatment |
| Correlation of total symptom burden with change in BMI-adjusted amplitude | 4 weeks | Correlation of total symptom burden with change in BMI-adjusted amplitude |
Countries
New Zealand
Outcome results
None listed