ANZCTR - Registration

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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Type 2 diabetes

Obesity

Condition category

Condition code

Metabolic and Endocrine

Diabetes

Diet and Nutrition

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]

Treatment: Drugs

Comparator / control treatment

Microcrystalline cellulose

Control group

Placebo

Outcomes

Primary outcome [1]

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]

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]

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]

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]

Difference in small intestinal transit time (caecal arrival time) between study days after GLY-200 and placebo treatment.

Timepoint [2]

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]

Differences in glucose absorption between study days after GLY-200 and placebo treatment.

Timepoint [3]

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]

Differences in serum bile acid profiles between study days after GLY-200 and placebo treatment.

Timepoint [4]

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]

Differences in serum FGF19 concentrations between study days after GLY-200 and placebo treatment.

Timepoint [5]

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]

Differences in plasma insulin concentrations between study days after GLY-200 and placebo treatment.

Timepoint [6]

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]

Differences in plasma C-peptide concentrations between study days after GLY-200 and placebo treatment.

Timepoint [7]

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]

Differences in plasma glucagon concentrations between study days after GLY-200 and placebo treatment.

Timepoint [8]

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]

Differences in plasma gastric inhibitory polypeptide (GIP) concentrations between study days after GLY-200 and placebo treatment.

Timepoint [9]

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]

Differences in plasma CCK concentrations between study days after GLY-200 and placebo treatment.

Timepoint [10]

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]

Differences in plasma GLP-1 concentrations between study days after GLY-200 and placebo treatment.

Timepoint [11]

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]

Differences in plasma PYY concentrations between study days after GLY-200 and placebo treatment.

Timepoint [12]

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]

Differences in gastrointestinal symptoms and appetite perceptions between study days after GLY-200 and placebo treatment.

Timepoint [13]

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]

Differences in energy intake between study days after GLY-200 and placebo treatment.

Timepoint [14]

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]

Differences in postprandial blood pressure and heart rate between study days after GLY-200 and placebo treatment.

Timepoint [15]

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

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]

Commercial sector/Industry

Name [1]

Glyscend Therapeutics

Country [1]

United States of America

Primary sponsor type

University

Name

The University of Adelaide

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Central Adelaide Local Health Network Human Research Ethics Committee

Ethics committee address [1]

Level 3, Roma Mitchell Building | 136 North Terrace, Adelaide, SA 5000

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

23/10/2023

Approval date [1]

12/12/2023

Ethics approval number [1]

2023/HRE00292

Summary

Brief summary

‘GLY-200' is an orally-administered, pH-dependent, gut-restricted therapeutic polymer developed by Glyscend Therapeutics. GLY-200 interacts with the mucus on the surface of the duodenum (the first part of the small intestine) to form a temporary barrier that lasts several hours. 

This mimics the effects of gastric bypass surgery – a very effective surgical procedure for type 2 diabetes and obesity – where the duodenum is removed from contact with meal contents.  

We don’t fully understand how excluding the duodenum from contact with nutrients results in lowering of blood glucose or body weight, but possible mechanisms include slowing of stomach emptying or passage of contents through the small intestine, reduction in glucose absorption from the duodenum, or changes in the levels of hormones secreted by the small intestine. 

This study is designed to investigate these possible mechanisms, in both healthy volunteers and people with type 2 diabetes treated only with diet or metformin.

Trial website

Public notes

Contacts

Principal investigator

Name

Prof Chris Ryaner

Address

Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000

Country

Australia

Phone

+61 8 8313 6693

Email

[email protected]

Contact person for public queries

Name

Chris Ryaner

Address

Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000

Country

Australia

Phone

+61 8 8313 6693

Email

[email protected]

Contact person for scientific queries

Name

Chris Ryaner

Address

Level 5 AHMS Building, The University of Adelaide, North Terrace, Adelaide, SA 5000

Country

Australia

Phone

+61 8 8313 6693

Email

[email protected]

Trial Review

Documents added manually

Documents added automatically