UMIN-CTR Clinical Trial

Basic information
Public title	Effects of Ipragliflozin on Body Weight in Japanese Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Insulin Therapy
Acronym	Effects of Ipragliflozin on Body Weight in Japanese Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Insulin Therapy(SUMS-ADDIT-1)
Scientific Title	Effects of Ipragliflozin on Body Weight in Japanese Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Insulin Therapy
Scientific Title:Acronym	Effects of Ipragliflozin on Body Weight in Japanese Patients with Type 2 Diabetes Mellitus with Inadequate Glycemic Control on Insulin Therapy(SUMS-ADDIT-1)
Region	Japan

Condition
Condition	Type 2 diabetes
Classification by specialty	Endocrinology and Metabolism
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To investigate the effects of ipragliflozin on changes in body weight from 0 to 24 weeks of Japanese patients with type 2 diabetes undergoing insulin therapy
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1
Trial characteristics_2
Developmental phase

Assessment
Primary outcomes	Changes in body weight from 0 to 24 weeks
Key secondary outcomes	Changes and percent changes of following parameters from 0 to 24 weeks 1) Physical findings - Systolic/diastolic blood pressure - Pulse 2) Body composition - Fat mass, lean body mass, and bone density measured by DEXA - Subcutaneous fat area at the umbilical level, visceral fat area at the umbilical level, iliopsoas muscle area, and volume of the liver measured by MRI - Intrahepatic fat mass and hepatic glycogen content measured by MRS - Visceral fat mass and subcutaneous fat mass measured by Dual Scan - Fat mass and muscle mass (right and left arms, right and left lower limbs, and body trunk) and water volume measured by weight scale and body composition scale 3) Glucose metabolism HbA1c, Fasting plasma glucose, 1,5 AG, Fasting CPR, Fasting urinary glucose, Glucagon 4) Lipid metabolism Total cholesterol, LDL cholesterol, HDL cholesterol, Blood triglyceride, Blood ketone bodies (total ketone body, ACAC, 3-OHBA), Free fatty acid in the blood, Free glycerol in the blood, RLP cholesterol 5) Liver function tests ALT, AST, Gamma-GTP, ChE, Ferritin 6) Others Albumin in urine, Serum uric acid, Urinary uric acid, Blood amino acid fraction, FGF-21, Cytokeratin-18, Oxidative stress marker (TBARS), Blood lipidomics, PBMC mRNA expression, Erythropoietin, Food preference

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	2
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	Oral administration of 50 mg ipragliflozin once daily for 24 weeks
Interventions/Control_2	Insulin therapy
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	75 years-old >
Gender	Male and Female
Key inclusion criteria	Poorly controlled, overweight outpatients with type 2 diabetes who undergoes insulin therapy 1) Aged >= 20, <75 at consent 2) Type 2 diabetes patients undergoing insulin therapy 3) HbA1c > 7.0% and < 10.0% 4) BMI > 23 kg/m2 5) eGFR > 45 ml/min/1.73m2 6) Outpatient 7) Provided written informed consent
Key exclusion criteria	1) Has history of receiving a SGLT-2 inhibitor 2) Contraindication to the use of ipragliflozin (history of hypersensitivity to ipragliflozin, or pregnant, etc.) 3) With severe ketosis, diabetic coma, or precoma 4) Has history of hospitalization for infection, trauma, or surgery within 6 months 5) With history or under treatment of brain infarction or transient ischemic attack 6) With an episode of angina pectoris or myocardial infarction within 6 months 7) Receiving loop diuretics 8) With orthostatic hypotension 9) Considered as inadequate by the investigator
Target sample size	52

Research contact person
Name of lead principal investigator	1st name Katsutaro Middle name Last name Morino
Organization	Shiga University of Medical Science
Division name	Department of Medicine
Zip code	520-2192
Address	Seta Tsukinowa-cho, Otsu-city, Shiga, Japan 520-2192
TEL	077-548-2222
Email	morino@belle.shiga-med.ac.jp

Public contact
Name of contact person	1st name Akio Middle name Last name Tsuji
Organization	Shiga University of Medical Science
Division name	Clinical Reseach and Development Center
Zip code	520-2192
Address	Seta Tsukinowa-cho, Otsu-city, Shiga, Japan 520-2192
TEL	077-548-3576
Homepage URL
Email	hqrec@belle.shiga-med.ac.jp

Sponsor
Institute	Shiga University of Medical Science
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
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Shiga University of Medical Science
Address	Seta Tsukinowa-cho, Otsu-city, Shiga, Japan 520-2192
Tel	077-548-3576
Email	hqrec@belle.shiga-med.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	滋賀医科大学医学部附属病院

Other administrative information
Date of disclosure of the study information	2015 Year 09 Month 01 Day

Related information
URL releasing protocol	https://onlinelibrary.wiley.com/doi/10.1111/jdi.12985
Publication of results	Unpublished

Result
URL related to results and publications	https://onlinelibrary.wiley.com/doi/10.1111/jdi.12985
Number of participants that the trial has enrolled	50
Results	BW change was significantly larger in the ipragliflozin group than in the control group (-2.78 vs -0.22 kg, P < 0.0001). Total fat mass was reduced evenly in the arms, lower limbs and trunk in the ipragliflozin group. Total muscle mass and bone mineral content were maintained, but muscle mass in the arms might have been affected by ipragliflozin treatment.
Results date posted	2019 Year 04 Month 30 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	Type 2 diabetes patients undergoing insulin therapy Japanese Aged >= 20, <75 at consent HbA1c > 7.0% and < 10.0% BMI > 23 kg/m2 eGFR > 45 ml/min/1.73m2
Participant flow	A total of 77 eligible patients with type 2 diabetes mellitus were screened at Shiga University of Medical Science Hospital. 50 were enrolled. After exclusion of one patient who withdrew consent because of breathing difficulty during MRI examination, 49 patients were randomly assigned to either the Ipra group (n = 25) or the Control group (n = 24). A total of 44 patients completed the study. One patient in the Ipra group withdrew consent before starting the intervention because of anxiety about ipragliflozin side effects. Two patients in the Ipra group discontinued the intervention, one because of exanthema and one because of liver dysfunction, but continued follow up, including bodyweight and body composition measurements. Two additional patients in the Ipra group withdrew from the intervention, one because of cholecystitis and one because of genital itching. Finally, 48 patients (Ipra, n = 24; Control, n = 24) were included in ITT analysis; however, two patients in the Ipra group were not followed up at 24 weeks and were not included in the primary analysis.
Adverse events	Hypoglycemia, dehydration, urinary tract infection, genital itching and exanthema were observed in both the Ipra and Control groups. Cholecystitis, gastric cancer, cataract surgery, bone fracture, and ileus were reported. All of them were incidental. The trial was continued with permission of the safety committee.
Outcome measures	Changes in body weight from 0 to 24 weeks Changes and percent changes of following parameters from 0 to 24 weeks 1) Physical findings - Systolic/diastolic blood pressure - Pulse 2) Body composition - Fat mass, lean body mass, and bone density measured by DEXA - Subcutaneous fat area at the umbilical level, visceral fat area at the umbilical level, iliopsoas muscle area, and volume of the liver measured by MRI - Intrahepatic fat mass and hepatic glycogen content measured by MRS - Visceral fat mass and subcutaneous fat mass measured by Dual Scan - Fat mass and muscle mass (right and left arms, right and left lower limbs, and body trunk) and water volume measured by weight scale and body composition scale 3) Glucose metabolism HbA1c, Fasting plasma glucose, 1,5 AG, Fasting CPR, Fasting urinary glucose, Glucagon 4) Lipid metabolism Total cholesterol, LDL cholesterol, HDL cholesterol, Blood triglyceride, Blood ketone bodies (total ketone body, ACAC, 3-OHBA), Free fatty acid in the blood, Free glycerol in the blood, RLP cholesterol 5) Liver function tests ALT, AST, Gamma-GTP, ChE, Ferritin 6) Others Albumin in urine, Serum uric acid, Urinary uric acid, Blood amino acid fraction, FGF-21, Cytokeratin-18, Oxidative stress marker (TBARS), Blood lipidomics, PBMC mRNA expression, Erythropoietin, Food preference
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Main results already published
Date of protocol fixation	2015 Year 07 Month 13 Day
Date of IRB	2015 Year 07 Month 28 Day
Anticipated trial start date	2015 Year 11 Month 30 Day
Last follow-up date	2017 Year 10 Month 25 Day
Date of closure to data entry
Date trial data considered complete	2017 Year 11 Month 29 Day
Date analysis concluded	2022 Year 09 Month 30 Day

Other
Other related information

Management information
Registered date	2015 Year 08 Month 28 Day
Last modified on	2022 Year 02 Month 24 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021790