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出境医 / 临床实验 / Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
Study Description
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Hyperinsulinemic Hypoglycemia Postprandial Hypoglycemia | Drug: ZP4207 Other: Placebo (saline) | Phase 2 |
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:
- Subcutaneous (sc) placebo (saline) injection
- Sc injection with 80 μg dasiglucagon
- Sc injection with 200 μg dasiglucagon
Study Design
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 10 participants |
| Allocation: | Randomized |
| Intervention Model: | Crossover Assignment |
| Intervention Model Description: | Double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass |
| Actual Study Start Date : | September 18, 2019 |
| Actual Primary Completion Date : | February 26, 2020 |
| Actual Study Completion Date : | February 26, 2020 |
Arms and Interventions
| Arm | Intervention/treatment |
|---|---|
|
Experimental: 80 ug of sc dasiglucagon
80 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
|
Drug: ZP4207
Abdominal SC administration
Other Name: Dasiglucagon
|
|
Experimental: 200 ug of sc dasiglucagon
200 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
|
Drug: ZP4207
Abdominal SC administration
Other Name: Dasiglucagon
|
|
Placebo Comparator: 0.4 mL of sc saline (placebo)
0.4 mL fluid (saline/placebo) is injected abdominal subcutaneous postprandial prior to hypoglycemia.
|
Other: Placebo (saline)
Abdominal SC administration
|
Outcome Measures
Primary Outcome Measures :
- Nadir plasma glucose concentration within two hundred forty minutes after MMT [ Time Frame: Two hundred forty minutes ]Nadir plasma glucose concentration within two hundred forty minutes after MMT
Secondary Outcome Measures :
- Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level [ Time Frame: Two hundred forty minutes ]Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level
- Time in hypoglycaemia (plasma glucose concentration <3.9 mmol/l) from study drug administration until 240 minutes [ Time Frame: Two hundred forty minutes ]Time in hypoglycaemia
- Time below fasting plasma glucose level from study drug administration until two hundred forty minutes [ Time Frame: Two hundred forty minutes ]Time below fasting plasma glucose level
- 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. [ Time Frame: Two hundred forty minutes ]Area 1
- 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. [ Time Frame: Two hundred forty minutes ]Area 2
- Edinburgh Hypoglycaemia Symptom Scale (EHSS) responses of the Edinburgh Hypoglycaemia Symptom Scale (EHSS) and early dumping symptoms based on [ Time Frame: t=zero to t=Two hundred forty minutes ]likert scale one (absent) to seven (severe)
- The Dumping Severity Score (DSS). [ Time Frame: t=zero to t=Two hundred forty minutes ]likert scale, zero (absent) to three (severe)
- Frequency and severity of adverse events and serious adverse events recorded during the meal test [ Time Frame: from t= minus thirty to t=Two hundred forty minutes ]Frequency
Eligibility Criteria
| Ages Eligible for Study: | 18 Years to 75 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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.
Contacts and Locations
Locations
| Denmark | |
| Center for Clinical Metabolic Research, Herlev-Gentofte Hospital | |
| Hellerup, Denmark, 2900 | |
Sponsors and Collaborators
University Hospital, Gentofte, Copenhagen
Investigators
| Principal Investigator: | Filip M. Knop, Prof., MD | Herlev-Gentofte Hospital, Center for Clinical Metabolic Research |
| Tracking Information | |||||
|---|---|---|---|---|---|
| First Submitted Date ICMJE | June 6, 2019 | ||||
| First Posted Date ICMJE | June 13, 2019 | ||||
| Last Update Posted Date | March 31, 2020 | ||||
| Actual Study Start Date ICMJE | September 18, 2019 | ||||
| Actual Primary Completion Date | February 26, 2020 (Final data collection date for primary outcome measure) | ||||
| Current Primary Outcome Measures ICMJE |
Nadir plasma glucose concentration within two hundred forty minutes after MMT [ Time Frame: Two hundred forty minutes ] Nadir plasma glucose concentration within two hundred forty minutes after MMT
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| Original Primary Outcome Measures ICMJE | Same as current | ||||
| Change History | |||||
| Current Secondary Outcome Measures ICMJE |
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| Original Secondary Outcome Measures ICMJE |
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| Current Other Pre-specified Outcome Measures | Not Provided | ||||
| Original Other Pre-specified Outcome Measures | Not Provided | ||||
| Descriptive Information | |||||
| Brief Title ICMJE | Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass | ||||
| Official Title ICMJE | Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass | ||||
| 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:
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| Study Type ICMJE | Interventional | ||||
| Study Phase ICMJE | Phase 2 | ||||
| Study Design ICMJE | Allocation: Randomized Intervention Model: Crossover Assignment Intervention Model Description: Double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days Masking: Double (Participant, Investigator)Primary Purpose: Treatment |
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| Condition ICMJE |
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| Intervention ICMJE |
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| Study Arms ICMJE |
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| Publications * | Not Provided | ||||
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* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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| Recruitment Information | |||||
| Recruitment Status ICMJE | Completed | ||||
| Actual Enrollment ICMJE |
10 | ||||
| Original Estimated Enrollment ICMJE | Same as current | ||||
| Actual Study Completion Date ICMJE | February 26, 2020 | ||||
| Actual Primary Completion Date | February 26, 2020 (Final data collection date for primary outcome measure) | ||||
| Eligibility Criteria ICMJE |
Inclusion Criteria:
Exclusion Criteria:
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| Sex/Gender ICMJE |
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| Ages ICMJE | 18 Years to 75 Years (Adult, Older Adult) | ||||
| Accepts Healthy Volunteers ICMJE | Yes | ||||
| Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||||
| Listed Location Countries ICMJE | Denmark | ||||
| Removed Location Countries | |||||
| Administrative Information | |||||
| NCT Number ICMJE | NCT03984370 | ||||
| Other Study ID Numbers ICMJE | CKN-DASI-RYGB 2019-001915-22 ( EudraCT Number ) |
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| Has Data Monitoring Committee | Yes | ||||
| U.S. FDA-regulated Product |
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| IPD Sharing Statement ICMJE |
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| Responsible Party | Filip Krag Knop, University Hospital, Gentofte, Copenhagen | ||||
| Study Sponsor ICMJE | University Hospital, Gentofte, Copenhagen | ||||
| Collaborators ICMJE | Not Provided | ||||
| Investigators ICMJE |
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| PRS Account | University Hospital, Gentofte, Copenhagen | ||||
| Verification Date | March 2020 | ||||
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ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |
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