Clinical trial NCT03984370: Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
Official title: Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hyperinsulinemic Hypoglycemia
Postprandial Hypoglycemia
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
First posted: 2019-06-13
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days
Primary purpose: TREATMENT

Brief summary: The aim of this study is investigating the effect of a novel glucagon analogue administration in gastric bypass operated individuals, who are reactive hypoglycemic.

Detailed description: The Roux-En-Y gastric bypass (RYGB) has major health-promoting effects - reversing type-2-diabetes, improving dyslipidemia and inducing robust weight loss. However, several RYGB-individuals, post surgery, suffers from dumping syndrome and postprandial hyperinsulinemic hypoglycemia (PHH) due to the anatomical rearrangement of the gastro-intestinal system. Dasiglugaon (also known as (ZP4207) has shown great pharmacokinetic- and dynamic effects, compared to other glucagon analogues on the market, when administrated to hypoglycemic type-1-diabetics.

Therefore we aim to examine the effects of two different doses of dasiglucagon on the postprandial nadir plasma glucose concentration in RYGB-operated individuals suffering from PHH by use of a mixed meal test (MMT).

The study is designed as a double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days in which participants will undergo an MMT along with one of the following double-blinded interventions:

1. Subcutaneous (sc) placebo (saline) injection
2. Sc injection with 80 μg dasiglucagon
3. Sc injection with 200 μg dasiglucagon

Eligibility criteria: Inclusion Criteria:

* Documented postprandial hypoglycaemia (\<3.9 mmol/l) by 6-day CGM or during a MMT
* Documented plasma glucose concentration excursions \>5.0 mmol/l by 6-day CGM or a MMT
* Haemoglobin levels for women \>7.3 mmol/l and for men \>8.3 mmol/l
* Ferritin \>10 μg/l
* Cobalamin \>150 pmol/l
* Fasting plasma glucose concentration within the range of 4.0-6.0 mmol/l CKN-DASI-RYGB protocol version 1.0 6
* Normal electrocardiogram (ECG)
* Negative urine human chorionic gonadotropin (hCG) (for fertile women)

Exclusion Criteria:

* Treatment with medication(s) affecting insulin secretion or any antidiabetic drugs
* Treatment with antipsychotics
* Current participation in another clinical trial with administration of investigational drug.
* Previous exposure to dasiglucagon (otherwise known as ZP4207)
* History of liver disease that is expected to interfere with the anti-hypoglycaemic action of glucagon (e.g. liver failure or cirrhosis).
* Pregnancy
* Breastfeeding
* Any factors that, in the opinion of the site principal investigator or clinical protocol chair, would interfere with the safe completion of the study, including medical conditions that may require hospitalization during the trial or allergy to the ingredients in the study drug.

Primary outcomes:
measure: Nadir plasma glucose concentration within two hundred forty minutes after MMT
timeFrame: Two hundred forty minutes
Secondary outcomes:
measure: Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level
timeFrame: Two hundred forty minutes
measure: Time in hypoglycaemia (plasma glucose concentration <3.9 mmol/l) from study drug administration until 240 minutes
timeFrame: Two hundred forty minutes
measure: Time below fasting plasma glucose level from study drug administration until two hundred forty minutes
timeFrame: Two hundred forty minutes
measure: Area 1: the area above the glucose curve and below the fasting level from the time of study drug administration until glucose values reach the fasting level.
timeFrame: Two hundred forty minutes
measure: Area 2: the area below the glucose curve and above the fasting level from the time glucose values reach the fasting level until 240 minutes.
timeFrame: Two hundred forty minutes
measure: Edinburgh Hypoglycaemia Symptom Scale (EHSS) responses of the Edinburgh Hypoglycaemia Symptom Scale (EHSS) and early dumping symptoms based on
timeFrame: t=zero to t=Two hundred forty minutes
measure: The Dumping Severity Score (DSS).
timeFrame: t=zero to t=Two hundred forty minutes
measure: Frequency and severity of adverse events and serious adverse events recorded during the meal test
timeFrame: from t= minus thirty to t=Two hundred forty minutes
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Clinical Metabolic Research, Herlev-Gentofte Hospital
Study officials:
affiliation: Herlev-Gentofte Hospital, Center for Clinical Metabolic Research
name: Filip M. Knop, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nielsen CK, Ohrstrom CC, Kielgast UL, Hansen DL, Hartmann B, Holst JJ, Lund A, Vilsboll T, Knop FK. Dasiglucagon Effectively Mitigates Postbariatric Postprandial Hypoglycemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. Diabetes Care. 2022 Jun 2;45(6):1476-1481. doi: 10.2337/dc21-2252.