UMIN-CTR Clinical Trial

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

Type 2 diabetes

Classification by specialty

Endocrinology and Metabolism

Classification by malignancy

Others

Genomic information

NO

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

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

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

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

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

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

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

Institute

Shiga University of Medical Science

Institute

Department

Personal name

Organization

Astellas Pharma Inc.

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

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

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

滋賀医科大学医学部附属病院

Date of disclosure of the study information

2015

Year

09

Month

01

Day

URL releasing protocol

https://onlinelibrary.wiley.com/doi/10.1111/jdi.12985

Publication of results

Unpublished

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

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 related information

Registered date

2015

Year

08

Month

28

Day

Last modified on

2022

Year

02

Month

24

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000021790