Hyperinsulinemic HypoglycemiaPhase 2NCT03984370
Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
A Phase 2 study testing ZP4207 in people with Hyperinsulinemic Hypoglycemia and Postprandial Hypoglycemia, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Hyperinsulinemic Hypoglycemia, Postprandial Hypoglycemia
- What is being tested?
- ZP4207
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteDenmark
- Study dates
- 18 Sep 2019to 26 Feb 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Clinical Metabolic Research, Herlev-Gentofte Hospital
Hellerup, 2900
About this study
The aim of this study is investigating the effect of a novel glucagon analogue administration in gastric bypass operated individuals, who are reactive hypoglycemic.
Read the 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
- Being tested
- ZP4207, Placebo (saline)
- Medical subject headings
- Congenital Hyperinsulinism, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZP4207Drug
Also called Dasiglucagon
Abdominal SC administration
Placebo (saline)Other
Abdominal SC administration
| Study group | Role | What they receive |
|---|---|---|
| 80 ug of sc dasiglucagon | Experimental | 80 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia. Receives: Drug: ZP4207 |
| 200 ug of sc dasiglucagon | Experimental | 200 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia. Receives: Drug: ZP4207 |
| 0.4 mL of sc saline (placebo) | Placebo comparator | 0.4 mL fluid (saline/placebo) is injected abdominal subcutaneous postprandial prior to hypoglycemia. Receives: Other: Placebo (saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nadir plasma glucose concentration within two hundred forty minutes after MMT
Nadir plasma glucose concentration within two hundred forty minutes after MMT
Measured: Two hundred forty minutes
Secondary outcomes (8)
Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level
Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level
Measured: Two hundred forty minutes
Time in hypoglycaemia (plasma glucose concentration <3.9 mmol/l) from study drug administration until 240 minutes
Time in hypoglycaemia
Measured: Two hundred forty minutes
Time below fasting plasma glucose level from study drug administration until two hundred forty minutes
Time below fasting plasma glucose level
Measured: Two hundred forty minutes
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.
Area 1
Measured: Two hundred forty minutes
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.
Area 2
Measured: Two hundred forty minutes
Edinburgh Hypoglycaemia Symptom Scale (EHSS) responses of the Edinburgh Hypoglycaemia Symptom Scale (EHSS) and early dumping symptoms based on
likert scale one (absent) to seven (severe)
Measured: t=zero to t=Two hundred forty minutes
The Dumping Severity Score (DSS).
likert scale, zero (absent) to three (severe)
Measured: t=zero to t=Two hundred forty minutes
Frequency and severity of adverse events and serious adverse events recorded during the meal test
Frequency
Measured: from t= minus thirty to t=Two hundred forty minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2019
- Study start18 Sep 2019
- Primary completion26 Feb 2020
- Study completion26 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hyperinsulinemic HypoglycemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Gentofte, Copenhagen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Filip Krag Knop, University Hospital, Gentofte, Copenhagen
- Investigators
- Filip M. Knop, Prof., MD, Principal investigator, Herlev-Gentofte Hospital, Center for Clinical Metabolic Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03984370
- Sponsor's protocol ID
- CKN-DASI-RYGB
- Other IDs
- 2019-001915-22, 2019
- Status last verified
- Mar 2020
- First submitted
- 6 Jun 2019
- Last updated
- 31 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35320361
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dasiglucagon in the Treatment of Postprandial Hypoglycaemia After Roux-en-Y Gastric Bypass
- ClinicalTrials.gov ID
- NCT03984370
- Acronym / sponsor ID
- CKN-DASI-RYGB
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University Hospital, Gentofte, CopenhagenUniversity, hospital or other
- Study start
- 18 Sep 2019 (actual)
- Primary completion
- 26 Feb 2020 (actual)
- Study completion
- 26 Feb 2020 (actual)
- First posted
- 13 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Subcutaneous (sc) placebo (saline) injection
- Sc injection with 80 μg dasiglucagon
- Sc injection with 200 μg dasiglucagon
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Double-blinded, randomised, 3-period, 3-treatment, crossover study comprising 3 separate treatment days
| Arm | Type | Receives |
|---|---|---|
| 80 ug of sc dasiglucagon | Experimental | Drug: ZP420780 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia. |
| 200 ug of sc dasiglucagon | Experimental | Drug: ZP4207200 ug of dasiglucagon in a 0.4 mL fluid (saline) is injected abdominal subcutaneous postprandial prior to hypoglycemia. |
| 0.4 mL of sc saline (placebo) | Placebo comparator | Other: Placebo (saline)0.4 mL fluid (saline/placebo) is injected abdominal subcutaneous postprandial prior to hypoglycemia. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ZP4207Also: DasiglucagonAbdominal SC administration | Drug | 200 ug of sc dasiglucagon, 80 ug of sc dasiglucagon |
| Placebo (saline)Abdominal SC administration | Other | 0.4 mL of sc saline (placebo) |
Primary outcome
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
8 secondary outcomes
Time from dasiglucagon administration to recovery (first plasma glucose value above the fasting plasma glucose level
Time frame: Two hundred forty minutes
Time in hypoglycaemia (plasma glucose concentration <3.9 mmol/l) from study drug administration until 240 minutes
Time frame: Two hundred forty minutes
Time below fasting plasma glucose level from study drug administration until two hundred forty minutes
Time frame: Two hundred forty minutes
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 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
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
The Dumping Severity Score (DSS).
Time frame: t=zero to t=Two hundred forty minutes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2020.
- Derived from this study: PubMed 35320361Nielsen 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Filip M. Knop, Prof., MD principal investigator
Herlev-Gentofte Hospital, Center for Clinical Metabolic Research
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ZP4207 in people with Hyperinsulinemic Hypoglycemia and Postprandial Hypoglycemia, run by University Hospital, Gentofte, Copenhagen at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Nadir plasma glucose concentration within two hundred forty minutes after MMT (time frame: Two hundred forty minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03984370, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2020.