UMIN-CTR Clinical Trial

Basic information
Public title	Study of glucagon response and its association with glycemic control and variability after administration of ipragliflozin as an adjunctive to insulin treatment in patients with type 1 diabetes (Suglat-AID): a single-arm, multicenter, open-label,prospective exploratory trial
Acronym	Suglat-AID
Scientific Title	Study of glucagon response and its association with glycemic control and variability after administration of ipragliflozin as an adjunctive to insulin treatment in patients with type 1 diabetes (Suglat-AID): a single-arm, multicenter, open-label, prospective exploratory trial
Scientific Title:Acronym	Suglat-AID
Region	Japan

Condition
Condition	type 1 diabetes
Classification by specialty	Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	This study aims to determine whether the fasting glucagon levels and the glucagon response to ingestion of a mixed meal are altered after administration of ipragliflozin as an adjunctive therapy to insulin treatment in patients with T1D. We will also investigate whether the glucagon responses under ipragliflozin treatment are associated with amelioration/deterioration in glycemic control and variability.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2
Developmental phase	Not applicable

Assessment
Primary outcomes	Change in fasting glucagon levels and glucagon responses to ingestion of a mixed meal between baseline and 12 weeks after the administration of ipragliflozin
Key secondary outcomes	Changes in the following items from baseline to 12 weeks after the administration of ipragliflozin; body weight, glycated hemoglobin (HbA1c), glycated albumin (GA), the required daily dose of insulin, values obtained from the mixed meal tolerance test (MMTT), albuminuria, advanced glycation end products (AGEs), diacron-reactive oxygen metabolites (d-ROMs), the glucose values (mean amplitude of glycemic excursions (MAGE) and the percentage of time in the targeted range (TIR; glucose levels 70-180 mg/dL), time below range (TBR; glucose levels <70 mg/dL), time above range (TAR; glucose levels >180 mg/dL)) obtained from the intermittently scanned continuous glucose monitoring (isCGM) system with FreeStyle Libre, the levels of serum beta-hydroxybutyrate, frequency of development of ketosis, all adverse events

Base
Study type	Observational

Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	Patients will be required to meet all of the following inclusion criteria: (1) Diagnosed with T1D by diabetologists based on the criteria of T1D defined by the Japan Diabetes Society. (2) Indicated for ipragliflozin as an adjunctive to insulin therapy due to an inability to achieve a good level of glycemic control (HbA1c >7.5%) despite receiving intensive insulin therapy with the use of isCGM. (3) Confirmed to have absolute insulin deficiency as defined by a fasting C-peptide concentration <0.6 ng/mL and/or an increment of C-peptide levels <0.6 ng/mL during the glucagon challenge test. (4) Using an isCGM system with FreeStyle Libre. (5) Outpatients. (6) Willingness to provide written informed consent.
Key exclusion criteria	Patients with any of the following will be excluded: (1) Use of any SGLT2 inhibitors within 12 months before enrollment. (2) A previous history of ketoacidosis within 12 months before enrollment. (3) An eating disorder. (4) Regular consumption of a low-carbohydrate diet. (5) Alcohol abuse or alcohol consumption >20 g/day. (6) Severe renal dysfunction defined as an estimated glomerular filtration rate <30 mL/min/1.73m2. (7) Severe anemia defined as a hemoglobin level <10 g/dL. (8) Hypersensitivity or allergy to SGLT2 inhibitors including ipragliflozin. (9) Body mass index (BMI) <20.0 kg/m2. (10) Previous history of repeated severe hypoglycemia, urinary tract infection or genital infection. (11) Pregnancy or breastfeeding. (12) HbA1c levels >11% at enrollment. (13) Judged inappropriate to participate by the study investigators.
Target sample size	24

Research contact person
Name of lead principal investigator	1st name Norio Middle name Last name Abiru
Organization	Nagasaki University Hospital
Division name	Department of Endocrinology and Metabolism
Zip code	852-8501
Address	1-7-1 Sakamoto Nagasaki, Japan
TEL	095-819-7262
Email	abirun@nagasaki-u.ac.jp

Public contact
Name of contact person	1st name Ichiro Middle name Last name Horie
Organization	Nagasaki University Hospital
Division name	Department of Endocrinology and Metabolism
Zip code	852-8501
Address	1-7-1 Sakamoto Nagasaki, Japan
TEL	095-819-7262
Homepage URL
Email	horie@nagasaki-u.ac.jp

Sponsor
Institute	Nagasaki University Hospital
Institute
Department

Funding Source
Organization	Astellas Pharma Inc.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor	Metabolic Signal Research Center, Institute for Molecular and Cellular Regulation, Gunma University Division of Diabetes, Endocrinology and Metabolism, Department of Internal Medicine, Hyogo College of Medicine Division of Diabetes and Endocrinology, Kumamoto Central Hospital The Department of Internal Medicine Division of Diabetes Endocrinology, Showa University Hospital Department of Interanl Medicine, Division of Diabetes and Endocrinology, Kobe University Graduate School of Medicine Minami Diabetes Clinical Research Center Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine
Name of secondary funder(s)

IRB Contact (For public release)
Organization	The Clinical Research Review Board in Nagasaki University
Address	1-7-1 Sakamoto Nagasaki-shi, Nagasaki-ken
Tel	095-819-7905
Email	gaibushikin@ml.nagasaki-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2020 Year 03 Month 24 Day

Related information
URL releasing protocol
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2020 Year 03 Month 23 Day
Date of IRB	2020 Year 03 Month 24 Day
Anticipated trial start date	2020 Year 06 Month 01 Day
Last follow-up date	2022 Year 06 Month 30 Day
Date of closure to data entry
Date trial data considered complete	2022 Year 07 Month 31 Day
Date analysis concluded	2022 Year 12 Month 31 Day

Other

Other related information

(1) Patient background:inital of patient, diagnosis of T1DM(Type 1A or Type 1B), sex, DoB, hight, body weight, diabetic complications(retinopathy, nephropathy,neuropathy), past histry, duration of diabetes, mediacal history of daibetes (2) Meal tolerant test(4weeks before and 12weeks after ipragliflozin treatment): Plasma level of glucose, C-peptide, glucagon, IRI, total ketone body, beta-hydroxybutyrate, AGE-related proteins, insulin antobody (3)Every visits: body weight, CBC, biochemical test(including HbA1c), urine test(including keton body), beta-hydroxybutyrate, %time in range and %time below range for last 4weeks by isCGM, self-monitoring of beta-hydroxybutyrate, adverse events

Management information
Registered date	2020 Year 02 Month 28 Day
Last modified on	2021 Year 06 Month 08 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000045194