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Trial registered on ANZCTR


Registration number
ACTRN12624000097549
Ethics application status
Approved
Date submitted
15/12/2023
Date registered
2/02/2024
Date last updated
21/07/2024
Date data sharing statement initially provided
2/02/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
GLY-200 for Duodenal Exclusion (GLYDE Study): Effects of GLY-200 in healthy humans and people with uncomplicated type 2 diabetes.
Scientific title
GLY-200 for Duodenal Exclusion (GLYDE Study): Effects of GLY-200 on plasma glucose concentrations, gastric emptying, small intestinal transit, glucose absorption (3-OMG), and insulin and gut hormones after a high carbohydrate semi-solid meal in healthy humans and people with uncomplicated type 2 diabetes.
Secondary ID [1] 311177 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 diabetes 332351 0
Obesity 332635 0
Condition category
Condition code
Metabolic and Endocrine 329061 329061 0 0
Diabetes
Diet and Nutrition 329339 329339 0 0
Obesity

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants who pass the screening visit will be randomised in a schedule determined by the Investigational Drugs Pharmacy, Royal Adelaide Hospital, in a double-blind, crossover design. After a 14-day run-in, including cessation of metformin for those usually metformin-treated, participants will undergo 2 treatment periods of 7 days each, separated by an interval of at least 14 days. The treatments will consist of GLY-200 2.0 g or placebo, given twice daily with 100 mL water, one hour before breakfast and dinner, provided in four matching gelatin capsules each containing 0.5 g GLY-200 or 0.5 g microcrystalline cellulose.

During each treatment period, and for 3 days before and after, participants will keep a daily record of upper gastrointestinal (GI) symptoms (using the Gastroparesis Cardinal Symptom Index Daily Diary (GCSI-DD)), and stool frequency and form (using the Bristol Stool Form Scale (BSFS)). Scores pertaining to the previous 24 hours will be recorded each evening, with daily reminder prompts by SMS. During each treatment week, participants will also have a daily telephone call with one of the investigators to reinforce compliance and monitor adverse events.

Participants will attend the clinical research facility (CRF) at Adelaide Health and Medical Science Building (AHMS) on the final day of each treatment period. On the evening preceding each of these study days (~1900h), participants will be given a standardised evening meal (McCain’s frozen beef lasagne (McCain Foods Proprietary Ltd, Victoria, Australia; or vegetarian lasagne for participants who are vegetarians) to consume with water. Following this meal, participants will be asked to fast from solids and liquids (water may be consumed until 10 pm) until the following morning, when they will attend the CRF of the AHMS building at 0800h.

On each study day, participants will attend the CRF at 0800h. Participants receiving treatment for hypertension will withhold their antihypertensive medication on the morning of the study. An intravenous cannula will be placed into a forearm vein for blood sampling (t = -80 min) and participants will then be seated with their back against a gamma camera. After 20 min quiet rest time to accommodate to laboratory conditions, participants will swallow the 4 capsules containing study drug or placebo, according to their current treatment phase, together with 100 mL water (t = -60 min).
At t = -5 min, participants will be given a mashed potato meal consisting of 65 g powdered mashed potato (Deb Instant; Continental, Sydney, Australia), 45 g margarine (Flora Original; Unilever, Sydney, Australia), 20 g glucose, 3 g of the non-metabolised glucose analogue 3-O-methylglucose (3-OMG), and 200 mL water, and the meal will be radiolabelled with 20 MBq 99mTc-calcium phytate. They will consume the meal over 5 min, together with a drink of 100 mL water. The meal will contain 2,687 kJ (642 kcal), with 72.3 g carbohydrate, 35.5 g fat, and 8.1 g protein.

Scintigraphic images will be acquired every minute for the first hour (t = 0 – 60 min), then at 3-min intervals for another 5 hours (t = 60 – 360 min). A left lateral image of the stomach will be acquired to correct for gamma-ray attenuation, and data will also be corrected for radioactive decay and subject movement. A region of interest will be drawn around the stomach, and percent retention determined at 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 210, 240, 270, 300, 330, and 360 min. The time taken for the stomach to empty 50% (T50) will also be calculated. Proximal and distal regions of the stomach will be defined, in order to evaluate intragastric meal distribution, as previously described. A region of interest will also be drawn around the colon using a composite image, and used to identify the caecal arrival time as a measure of small intestinal transit.

Blood will be sampled from the intravenous (IV) cannula, with the arm kept warm with a heat pad, at t = -65, -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min (20 mL per time point, total 220 mL per study day). Gastrointestinal symptoms and appetite perceptions will be monitored using 100mm visual analogue scales at the same intervals as blood sampling. Heart rate and blood pressure will also be monitored every 15 min throughout the study, increasing to every 5 min during t = 0 to 120 min, by an automated sphygmomanometer. The mean of the 3 fasting measurements preceding the meal will be used as a baseline.

At t = 360 min, a buffet meal will be provided from which participants will be allowed to eat as much as they wish for 30 min, from which energy intake will be quantified. The IV cannula will then be removed and participants will be able to leave the facility.
Intervention code [1] 327621 0
Treatment: Drugs
Comparator / control treatment
Microcrystalline cellulose
Control group
Placebo

Outcomes
Primary outcome [1] 336868 0
Difference in blood glucose (area under the curve (AUC) from 0 to 360 min) between study days after GLY-200 and placebo treatment.
Timepoint [1] 336868 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [1] 429953 0
Differences in gastric meal retention (%) over time, gastric half-emptying time and intra-gastric meal distribution between study days after GLY-200 and placebo treatment.
Timepoint [1] 429953 0
t = 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 210, 240, 270, 300, 330, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [2] 429954 0
Difference in small intestinal transit time (caecal arrival time) between study days after GLY-200 and placebo treatment.
Timepoint [2] 429954 0
t = 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 210, 240, 270, 300, 330, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [3] 429955 0
Differences in glucose absorption between study days after GLY-200 and placebo treatment.
Timepoint [3] 429955 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [4] 429956 0
Differences in serum bile acid profiles between study days after GLY-200 and placebo treatment.
Timepoint [4] 429956 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [5] 429957 0
Differences in serum FGF19 concentrations between study days after GLY-200 and placebo treatment.
Timepoint [5] 429957 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [6] 429958 0
Differences in plasma insulin concentrations between study days after GLY-200 and placebo treatment.
Timepoint [6] 429958 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [7] 429959 0
Differences in plasma C-peptide concentrations between study days after GLY-200 and placebo treatment.
Timepoint [7] 429959 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [8] 429960 0
Differences in plasma glucagon concentrations between study days after GLY-200 and placebo treatment.
Timepoint [8] 429960 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [9] 429961 0
Differences in plasma gastric inhibitory polypeptide (GIP) concentrations between study days after GLY-200 and placebo treatment.
Timepoint [9] 429961 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [10] 429962 0
Differences in plasma CCK concentrations between study days after GLY-200 and placebo treatment.
Timepoint [10] 429962 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [11] 429963 0
Differences in plasma GLP-1 concentrations between study days after GLY-200 and placebo treatment.
Timepoint [11] 429963 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [12] 429964 0
Differences in plasma PYY concentrations between study days after GLY-200 and placebo treatment.
Timepoint [12] 429964 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [13] 429965 0
Differences in gastrointestinal symptoms and appetite perceptions between study days after GLY-200 and placebo treatment.
Timepoint [13] 429965 0
t = -10, 15, 30, 60, 90, 120, 180, 240, 300, and 360 min on the last day of the treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [14] 429966 0
Differences in energy intake between study days after GLY-200 and placebo treatment.
Timepoint [14] 429966 0
Energy intake will be assessed by a buffet meal test during t = 360 to 420 min on the last day of treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.
Secondary outcome [15] 429967 0
Differences in postprandial blood pressure and heart rate between study days after GLY-200 and placebo treatment.
Timepoint [15] 429967 0
t = 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210, 225, 240, 255, 270, 285, 300, 315, 330, 345 and 360 min on the last day of treatment period 1 and period 2.
t = -60 is when capsules containing the study drug or placebo were given and t = -5 is when the mashed potato meal is given.

Eligibility
Key inclusion criteria
Healthy Volunteers
• Healthy males and females aged between 40 to 79 years
• Body mass index (BMI) between 19 to 32 kg/m2
• HbA1c less than 5.7%
• Fasting blood glucose less than 5.6 mmol/L

T2D patients
• Type 2 diabetes (T2D, World Health Organisation criteria)
• Males and females aged from 40 to 79 years
• BMI from 20 to 40 kg/m2 (i.e. a higher range than in the healthy participants to allow for the greater tendency for overweight/obesity in people with T2D)
• HbA1c less than 8.5% on stable (over 3 months) treatment with diet and/or metformin alone
Minimum age
40 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Use of any medication that may influence gastrointestinal motor function, body weight or appetite (opiates, anticholinergics, levodopa, clonidine, nitrates, phosphodiesterase type 5 inhibitors, sumatriptan, GLP-1 receptor agonists, metoclopramide, domperidone, prucalopride, or erythromycin)
• Use of medications that raise gastric pH, including proton pump inhibitors and H2 receptor antagonists
• Evidence of drug abuse, or consumption of more than 20 g alcohol, or 10 cigarettes, daily
• History of gastrointestinal disease, including significant upper or lower gastrointestinal symptoms (once weekly or more, or any history of swallowing difficulties, on the Digestive Health and Wellbeing Survey Short Form) or previous gastrointestinal surgery (other than uncomplicated appendicectomy or cholecystectomy)
• History of any form of heart disease or symptoms of syncope or pre-syncope (including feeling lightheaded or dizzy, feeling unsteady when standing, unexplained falls, fainting, unexplained changes in vision, such as blurring or tunnel vision)
• Other significant illness, including epilepsy or respiratory disease
• Haemoglobin below the lower limit of the normal range (ie. less than 135 g/L for men and 115 g/L for women), and ferritin below the lower limit of normal (ie. less than 30 mg/mL)
• Impaired renal or liver function (as assessed by calculated estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m2 or abnormal liver function tests (more than 1.5 times upper limit of normal range))
• Donation of blood within the previous 3 months
• Participation in any other research studies within the previous 3 months
• Exposure to ionising radiation for research purposes that exceeds 3.5 mSv within the previous 12 months
• Inability to give informed consent
• Female participants who are pregnant or planning for pregnancy, or are lactating

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2024
Actual
Date of last participant enrolment
Anticipated
2/02/2026
Actual
Date of last data collection
Anticipated
31/03/2026
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 315435 0
Commercial sector/Industry
Name [1] 315435 0
Glyscend Therapeutics
Country [1] 315435 0
United States of America
Primary sponsor type
University
Name
The University of Adelaide
Address
Clinical Research Facility, Level 4 Adelaide Health and Medical Sciences (AHMS) Building, North Terrace, Adelaide, SA 5000
Country
Australia
Secondary sponsor category [1] 317503 0
None
Name [1] 317503 0
Address [1] 317503 0
Country [1] 317503 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314345 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 314345 0
Ethics committee country [1] 314345 0
Australia
Date submitted for ethics approval [1] 314345 0
23/10/2023
Approval date [1] 314345 0
12/12/2023
Ethics approval number [1] 314345 0
2023/HRE00292

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131262 0
Prof Chris Ryaner
Address 131262 0
Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 131262 0
Australia
Phone 131262 0
+61 8 8313 6693
Fax 131262 0
Email 131262 0
[email protected]
Contact person for public queries
Name 131263 0
Chris Ryaner
Address 131263 0
Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 131263 0
Australia
Phone 131263 0
+61 8 8313 6693
Fax 131263 0
Email 131263 0
[email protected]
Contact person for scientific queries
Name 131264 0
Chris Ryaner
Address 131264 0
Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000
Country 131264 0
Australia
Phone 131264 0
+61 8 8313 6693
Fax 131264 0
Email 131264 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The ethical statement and informed consent do not allow for free data availability.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.