Type1 Diabetes MellitusPhase 1NCT03704818
Dapagliflozin Effects on Hypoglycemia
A Phase 1 study testing Dapagliflozin 5mg in people with Type1 Diabetes Mellitus, run by University of California, San Diego at 1 site in United States.
Trial summary
The purpose of this research study will be to test and evaluate if dapagliflozin has an effect on the amount of glucagon (a hormone produced by the pancreas and stomach that stimulates liver glucose production) produced by the body and if that change will improve recovery time from hypoglycemia (low blood sugar) in… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Type1 Diabetes Mellitus
- What is being tested?
- Dapagliflozin 5mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Oct 2018to 30 Nov 2021
- Phase
- Phase 1
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated written informed consent by the date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation
- Male or female patient receiving insulin for the treatment of documented diagnosis of T1DM for at least 1 year at the time of Visit 1
- Non-fasting C-peptide < 0.7 ng/mL at Visit 1
- HbA1c ≤ 10.0% at Visit 1
- Based on the Investigator's judgment patient must have a good understanding of his/her disease and how to manage it, and be willing and capable of performing the following study assessments (assessed at Visits 1):
- patient-led management and adjustment of insulin therapy
Show all 14Show fewer
- reliable approach to insulin dose adjustment for meals, such as carbohydrate counting
- reliable and regular home-based blood glucose monitoring
- be able to perform ketone sample measurement when feeling ill and/or nauseated
- implementation of an established "sick day" management regimen
- Age ≥ 18 and ≤ 70 years at Visit 1
- Body Mass Index (BMI) of 18.5 kg/m2 to 35.0 kg/m2 at Visit 1
- eGFR ≥ 60 mL/min/1.73m²
- Patients must be able and willing to perform study assessments
Who cannot join
- History of T2DM, maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis
- Pancreas, pancreatic islet cells or renal transplant recipient
- T1DM treatment with any other antihyperglycemic drug (e.g. metformin, alpha- glucosidase inhibitors, SGLT-2 inhibitors, pramlintide, inhaled insulin, pre-mixed insulins, etc.) within 30 days of run-in (visit 2)
- Occurrence of severe hypoglycemia involving coma and/or seizure that required hospitalization or hypoglycemia-related treatment by an emergency physician or paramedic within 3 months prior to Visit 1 or Visit 2
- Occurrence of DKA within 3 months prior to Visit 1 or Visit 2
- Acute coronary syndrome (non-STEMI, STEMI and unstable angina pectoris), stroke or transient ischemic attack (TIA) within 3 months prior to Visit 1 or Visit 2
Show all 15Show fewer
- Indication of liver disease, defined by serum levels of either alanine transaminase (ALT), aspartate transaminase (AST), or alkaline phosphatase above 3 x upper limit of normal (ULN) at Visit 1
- Current signs and symptoms of anemia accompanied by a hemoglobin laboratory value at or below 10.0 g/dL at screening.
- Eating disorders such as bulimia or anorexia nervosa
- Treatment with systemic corticosteroids within 30 days of run-in (visit 2), or planned initiation of such therapy at Visit 1 or Visit 2. Inhaled or topical use of corticosteroids (e.g. for asthma/chronic obstructive pulmonary disease) is acceptable.
- Medical history of cancer or treatment for cancer in the last five years prior to Visit 1. Resected basal cell carcinoma considered cured is exempted.
- Women who are pregnant, nursing, or who plan to become pregnant while in the trial
- Intake of an investigational drug in another trial within 30 days prior to Visit 1
- Patient not able to understand and comply with study requirements, based on Investigator's judgment
- Any other clinical condition that, based on Investigator's judgment, would jeopardize patient safety during trial participation or would affect the study outcome (e.g. immunocompromised patients who might be at higher risk of developing genital or mycotic infections, patients with chronic viral infections etc.)
Trial locations and contacts
1 site in 1 country.
United States1 site
UC San Diego Altman Clinical & Translational Research Institute
La Jolla, California, 92037
About this study
Official title: Evaluating the Effect of Dapagliflozin, an SGLT-2 Inhibitor, on the Counterregulatory Response to Hypoglycemia in Individuals With Type 1 Diabetes
The purpose of this research study will be to test and evaluate if dapagliflozin has an effect on the amount of glucagon (a hormone produced by the pancreas and stomach that stimulates liver glucose production) produced by the body and if that change will improve recovery time from hypoglycemia (low blood sugar) in participants with Type 1 Diabetes.
Read the detailed description
The purpose of this research study will be to test and evaluate if dapagliflozin has an effect on the amount of glucagon (a hormone produced by the pancreas and stomach that stimulates liver glucose production) produced by the body and if that change will improve recovery time from hypoglycemia (low blood sugar) in participants with Type 1 Diabetes. The study is a blinded, placebo-controlled, crossover design, where participants will receive dapagliflozin during one treatment period and placebo during a separate treatment period with neither the study team nor participants knowing what they are receiving at any given time. Participants will have 9 clinic visits over the course of 14-16 weeks, with 3 of those visits being overnight stays. The overnight stays are intended to control blood sugars in a normal state throughout the night and then participants will complete a hypoglycemic challenge the following morning. The body's response to the hypoglycemic challenge will provide the information needed to determine if dapagliflozin had an effect on recovery time from hypoglycemia.
- Conditions
- Type1 Diabetes Mellitus
- Being tested
- Dapagliflozin 5mg, Placebo Oral Tablet
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 5mgDrug
Also called Farxiga
Dapagliflozin treatment taken daily for 4-weeks.
Placebo Oral TabletDrug
Placebo treatment taken daily for 4-weeks.
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin 5mg | Experimental | Not described Receives: Drug: Dapagliflozin 5mg |
| Placebo | Experimental | Not described Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucagon Response to Hypoglycemia
Participants will undergo a baseline hypoglycemic clamp during which glucagon will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing glucagon.
Measured: 12 Weeks
Epinephrine Response to Hypoglycemia
Participants will undergo a baseline hypoglycemic clamp during which epinephrine will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing epinephrine.
Measured: 12 Weeks
Norepinephrine Response to Hypoglycemia
Participants will undergo a baseline hypoglycemic clamp during which norepinephrine will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing norepinephrine.
Measured: 12 Weeks
Cortisol Response to Hypoglycemia
Participants will undergo a baseline hypoglycemic clamp during which cortisol will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing cortisol.
Measured: 12 Weeks
Growth Hormone Response to Hypoglycemia
Participants will undergo a baseline hypoglycemic clamp during which growth hormone will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing growth hormone.
Measured: 12 Weeks
Hypoglycemia Awareness
Participants will undergo a baseline hypoglycemic clamp during which they will complete the Edinburgh Hypoglycemia Scale (EHS). Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing the EHS.
Measured: 12 Weeks
Trails Making B Performance Response to Hypoglycemia
Participants will undergo a baseline hypoglycemic clamp during which they will complete the cognitive test, Trails Making B. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing Trails Making B.
Measured: 12 Weeks
Digit Symbol Substitution Performance Response to Hypoglycemia
Participants will undergo a baseline hypoglycemic clamp during which they will complete the cognitive test, Digit Symbol Substitution. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing Digit Symbol Substitution.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2018
- Study start8 Oct 2018
- Primary completion30 Jun 2021
- Study completion30 Nov 2021
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 Type1 Diabetes MellitusStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Responsible party
- Principal investigator, Jeremy Pettus, MD, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03704818
- Sponsor's protocol ID
- UC-MEDJP-01
- Status last verified
- Jan 2024
- First submitted
- 8 Oct 2018
- Last updated
- 23 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Boeder SC, Gregory JM, Giovannetti ER, Pettus JH. SGLT2 Inhibition Increases Fasting Glucagon but Does Not Restore the Counterregulatory Hormone Response to Hypoglycemia in Participants With Type 1 Diabetes. Diabetes. 2022 Mar 1;71(3):511-519. doi: 10.2337/db21-0769.
PubMed 34857545
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Effect of Dapagliflozin, an SGLT-2 Inhibitor, on the Counterregulatory Response to Hypoglycemia in Individuals With Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT03704818
- Acronym / sponsor ID
- UC-MEDJP-01
- Conditions
- Type1 Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Juvenile Diabetes Research Foundation
- Study start
- 8 Oct 2018 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Nov 2021 (actual)
- First posted
- 15 Oct 2018 (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 purpose of this research study will be to test and evaluate if dapagliflozin has an effect on the amount of glucagon (a hormone produced by the pancreas and stomach that stimulates liver glucose production) produced by the body and if that change will improve recovery time from hypoglycemia (low blood sugar) in participants with Type 1 Diabetes.
Detailed description
The purpose of this research study will be to test and evaluate if dapagliflozin has an effect on the amount of glucagon (a hormone produced by the pancreas and stomach that stimulates liver glucose production) produced by the body and if that change will improve recovery time from hypoglycemia (low blood sugar) in participants with Type 1 Diabetes. The study is a blinded, placebo-controlled, crossover design, where participants will receive dapagliflozin during one treatment period and placebo during a separate treatment period with neither the study team nor participants knowing what they are receiving at any given time. Participants will have 9 clinic visits over the course of 14-16 weeks, with 3 of those visits being overnight stays. The overnight stays are intended to control blood sugars in a normal state throughout the night and then participants will complete a hypoglycemic challenge the following morning. The body's response to the hypoglycemic challenge will provide the information needed to determine if dapagliflozin had an effect on recovery time from hypoglycemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin 5mg | Experimental | Drug: Dapagliflozin 5mg |
| Placebo | Experimental | Drug: Placebo Oral Tablet |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Signed and dated written informed consent by the date of Visit 1 in accordance with Good Clinical Practice (GCP) and local legislation
- Male or female patient receiving insulin for the treatment of documented diagnosis of T1DM for at least 1 year at the time of Visit 1
- Non-fasting C-peptide < 0.7 ng/mL at Visit 1
- HbA1c ≤ 10.0% at Visit 1
- Based on the Investigator's judgment patient must have a good understanding of his/her disease and how to manage it, and be willing and capable of performing the following study assessments (assessed at Visits 1):
Key exclusion criteria (15 listed)
- History of T2DM, maturity onset diabetes of the young (MODY), pancreatic surgery or chronic pancreatitis
- Pancreas, pancreatic islet cells or renal transplant recipient
- T1DM treatment with any other antihyperglycemic drug (e.g. metformin, alpha- glucosidase inhibitors, SGLT-2 inhibitors, pramlintide, inhaled insulin, pre-mixed insulins, etc.) within 30 days of run-in (visit 2)
- Occurrence of severe hypoglycemia involving coma and/or seizure that required hospitalization or hypoglycemia-related treatment by an emergency physician or paramedic within 3 months prior to Visit 1 or Visit 2
- Occurrence of DKA within 3 months prior to Visit 1 or Visit 2
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 |
|---|---|---|
| Dapagliflozin 5mgAlso: FarxigaDapagliflozin treatment taken daily for 4-weeks. | Drug | Dapagliflozin 5mg |
| Placebo Oral TabletPlacebo treatment taken daily for 4-weeks. | Drug | Placebo |
Primary outcome
Glucagon Response to Hypoglycemia
Time frame: 12 Weeks
Participants will undergo a baseline hypoglycemic clamp during which glucagon will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing glucagon.
Epinephrine Response to Hypoglycemia
Time frame: 12 Weeks
Participants will undergo a baseline hypoglycemic clamp during which epinephrine will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing epinephrine.
Norepinephrine Response to Hypoglycemia
Time frame: 12 Weeks
Participants will undergo a baseline hypoglycemic clamp during which norepinephrine will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing norepinephrine.
Cortisol Response to Hypoglycemia
Time frame: 12 Weeks
Participants will undergo a baseline hypoglycemic clamp during which cortisol will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing cortisol.
Growth Hormone Response to Hypoglycemia
Time frame: 12 Weeks
Participants will undergo a baseline hypoglycemic clamp during which growth hormone will be measured. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing growth hormone.
Hypoglycemia Awareness
Time frame: 12 Weeks
Participants will undergo a baseline hypoglycemic clamp during which they will complete the Edinburgh Hypoglycemia Scale (EHS). Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing the EHS.
Trails Making B Performance Response to Hypoglycemia
Time frame: 12 Weeks
Participants will undergo a baseline hypoglycemic clamp during which they will complete the cognitive test, Trails Making B. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing Trails Making B.
Digit Symbol Substitution Performance Response to Hypoglycemia
Time frame: 12 Weeks
Participants will undergo a baseline hypoglycemic clamp during which they will complete the cognitive test, Digit Symbol Substitution. Follow-up hypoglycemic clamps will be performed after each 4-week treatment period re-assessing Digit Symbol Substitution.
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 23 Jan 2024.
- Derived from this study: PubMed 34857545Boeder SC, Gregory JM, Giovannetti ER, Pettus JH. SGLT2 Inhibition Increases Fasting Glucagon but Does Not Restore the Counterregulatory Hormone Response to Hypoglycemia in Participants With Type 1 Diabetes. Diabetes. 2022 Mar 1;71(3):511-519. doi: 10.2337/db21-0769.
- Individual participant dataSharing planned: No
Related trials for Type1 Diabetes Mellitus
Active, not recruitingPhase 3
Clinical Application of Stem Cell Educator Therapy in Type 1 Diabetes
Type 1 Diabetes
RecruitingObservational study
Study of High Density Lipoprotein Function in Type 1 Diabetic Patients With Nephropathy
Type 1 Diabetes
Recruiting
Supporting Medtronic 780G Insulin Pump Adoption in Latino Patients: A Spanish - Language Training Initiative
Diabetes Mellitus, Type 1 Diabetes
Recruiting
Closed Loop and Education for Hypoglycemia Awareness Restoration
Diabetes Mellitus, Type 1
Not yet recruiting
Care COMPASS Study
Diabetes Mellitus ( Type 1 and Type 2), Hypertension
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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dapagliflozin 5mg in people with Type1 Diabetes Mellitus, run by University of California, San Diego at 1 site in United States.
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 14 inclusion and 15 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 23 Jan 2024. 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 United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Glucagon Response to Hypoglycemia (time frame: 12 Weeks). The study lists 8 primary outcomes in all. 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 NCT03704818, 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 23 Jan 2024.