- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03704818
Dapagliflozin Effects on Hypoglycemia
January 19, 2024 updated by: Jeremy Pettus, MD, University of California, San Diego
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
22
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
California
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La Jolla, California, United States, 92037
- UC San Diego Altman Clinical & Translational Research Institute
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- 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
- 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
Exclusion Criteria:
- 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
- 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.)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Placebo
|
Placebo treatment taken daily for 4-weeks.
|
Experimental: Dapagliflozin 5mg
|
Dapagliflozin treatment taken daily for 4-weeks.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
12 Weeks
|
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.
|
12 Weeks
|
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.
|
12 Weeks
|
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.
|
12 Weeks
|
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.
|
12 Weeks
|
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.
|
12 Weeks
|
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.
|
12 Weeks
|
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.
|
12 Weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 8, 2018
Primary Completion (Actual)
June 30, 2021
Study Completion (Actual)
November 30, 2021
Study Registration Dates
First Submitted
October 8, 2018
First Submitted That Met QC Criteria
October 11, 2018
First Posted (Actual)
October 15, 2018
Study Record Updates
Last Update Posted (Actual)
January 23, 2024
Last Update Submitted That Met QC Criteria
January 19, 2024
Last Verified
January 1, 2024
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Immune System Diseases
- Autoimmune Diseases
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Hypoglycemia
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Sodium-Glucose Transporter 2 Inhibitors
- Dapagliflozin
Other Study ID Numbers
- UC-MEDJP-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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