HypoBar I: Delaying intestinal glucose absorption to ameliorate post-bariatric hypoglycaemia. A randomized cross-over clinical trial.

Phase 1

• Conditions: Post-bariatric hypoglycaemia; Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

• Registration Number: EUCTR2022-000157-87-DK
• Lead Sponsor: Hvidovre Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-01-24
• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

At enrolment, participants must:
•Be adults (above 18 years old);
•Have undergone bariatric surgery more than 18 months prior to inclusion;
•Self-reported weight stability (less than 5% variation over the 6 months);
•Present at least one 5-minutes or longer event of interstitial fluid glucose <3.0 mmol/L, one 5-minutes symptomatic event of IFG<3.9mmol/L (allowing a time gap between symptoms reported and low glucose values of ±30 minutes) at least 4.0% of IFG <3.9mmol/L during a min 10 days CGM monitoring screening period, excluding first 24 hours of monitoring (prone to error due to local inflammatory reaction);
•Have a negative pregnancy test, if applicable;
•Commit to safe contraception during the trial and over the following 5 months, namely intrauterine devices, hormonal contraception (oral contraceptive pills, implants, transdermal patches, vaginal rings or long-acting injections) or double barrier methods (a condom combined with a diaphragm).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

All patients presenting one of the following at enrolment will be excluded:
•Altered baseline analytical profile, namely an early morning 12h-fasting blood test with hemogram, liver and kidney functions tests, albumin, total proteins, plasma glucose, TSH, insulin, C-peptide, and beta-hCG and thus pointing towards other potential causes for hypoglycaemia and/or prone to unsafety to pursue the trial*;
•Inability or unwillingness to perform meal test (e.g. unable to have the meal over 20 minutes);
•Pharmacotherapy that affects glucose metabolism:
•Glucocorticoid treatment within 6 weeks of inclusion;
•Somatostatin analogue treatment within 4 months of inclusion;
•GLP-1 receptor analogue treatment within 6 half-lives of inclusion;
•SGLT2 inhibitor treatment within 2 weeks of inclusion.
•HbA1c >47.5 mmol/mol [>6.5%;]
•Antithyroid treatment within 3 months of inclusion or poorly managed thyroid disease (TSH outside reference range);
•Pregnancy (positive pregnancy test), aspiring to get pregnant over the following 5 months or lactation;
•Renal insufficiency (eGFR <60 ml/min/1.73m2);
•Elevation of liver enzymes (>3 x elevation of upper normal limit of alanine amino transferase and/or alkaline phosphatases);
•Poorly controlled psychiatric disease or mental retardation;
•Alcohol or other substance abuse;
•Significant anaemia (Hb <6.0 mmol/L);
•Recent history of major adverse cardiovascular events (MACE), such as hospitalizations for heart failure, nonfatal stroke, or nonfatal myocardial infarction within the previous 12 months;
•Any other condition that in the opinion of the investigator may compromise outcome;
•Sustained intolerance to study drugs.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate whether canagliflozin/acarbose therapy is an effective treatment for post-bariatric hypolgycaemia (PBH).;Secondary Objective: To explore how chronic treatment with canagliflozin/acarbose modulates the response to a standard meal; <br>To clarify if there is a correlation between PBH symptomatology, glycaemic variability and electrocardiographic findings, and whether these are modulated by treatment interventions.<br>;Primary end point(s): oTime under level 1 hypoglycaemia (IFG <3.9 mmol/L or <70 mg/dL) throughout CGM evaluation, comparing treatment intervention A (canagliflozin) and B (acarbose) against treatment intervention C (placebo).;Timepoint(s) of evaluation of this end point: Last 10-14 days of each treatment intervention.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Time under level 2 hypoglycaemia (IFG <3.0 mmol/L or <54 mg/dL) throughout CGM evaluation, comparing treatment interventions A and B against C;<br>- Postprandial nadir glucose during the meal test, comparing treatment interventions A and B against C;;Timepoint(s) of evaluation of this end point: Last 10-14 days of each treatment intervention.