UMIN-CTR Clinical Trial

Public title

anti-albuminuric effect of 1ow-dose spironolactone in patients with diabetic nephropathy

Acronym

anti-albuminuric effect of 1ow-dose spironolactone in patients with diabetic nephropathy

Scientific Title

anti-albuminuric effect of 1ow-dose spironolactone in patients with diabetic nephropathy

Scientific Title:Acronym

anti-albuminuric effect of 1ow-dose spironolactone in patients with diabetic nephropathy

Region

Japan

Condition

diabetic nephropathy

Classification by specialty

Endocrinology and Metabolism

Nephrology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

we aim to prove the anti-albuminuric effect and safety of spironolactone 12.5mg once daily compared with controls in patients with diabetic nephropathy

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

reduction in the rate of albuminuria at 24 weeks after administration.

Key secondary outcomes

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

No treatment

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

spironolactone 12.5mg once a day for 24 weeks.

Interventions/Control_2

control

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

Not applicable

Gender

Male and Female

Key inclusion criteria

1.patients with daiabetes who were 20year old or older
2.outpatients with diabetic nephropathy and albuminuria(more than 30 mg/g Cr)
3.eGFR more than 30mL/min/1.73m2
4.patients treated with RAS(renin-angiotensin system)blockade for more than 180 days
5.patients who were obtained written informed consent by free will after enough explanation.

Key exclusion criteria

1.eGFR less than 30mL/min/1.73m2
2.patients with potassium more than 5.0mEq/l
3.patients who have already treated with spironolactone
4.patients who have an allergy career to a study drug
5.pregnant woman and the woman whom I am nursing
6.other conditions that are considered inappropriate to participate by the investigators

Target sample size

130

Name of lead principal investigator

1st name	Ako
Middle name
Last name	Oiwa

Organization

Shinshu University Hospital

Division name

Diabetes, Endocrinology and Metabolism

Zip code

390-8621

Address

3-1-1 Asahi, Matumoto-shi, Nagano, JAPAN

TEL

0263-37-2686

Email

akooiwa@shinshu-u.ac.jp

Name of contact person

1st name	Ako
Middle name
Last name	Oiwa

Organization

Shinshu University Hospital

Division name

Diabetes, Endocrinology and Metabolism

Zip code

390-8621

Address

3-1-1 Asahi, Matumoto-shi, Nagano, JAPAN

TEL

0263-37-2686

Homepage URL

Email

akooiwa@shinshu-u.ac.jp

Institute

Diabetes, Endocrinology and Metabolism,
Shinshu University Hospital

Institute

Department

Personal name

Organization

Diabetes, Endocrinology and Metabolism,
Shinshu University Hospital

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Takeda Clinic of Internal Medicine
Miyamoto Clinic of Internal Medicine

Name of secondary funder(s)

Organization

Ethics Committee Secretariat, Shinshu University Hospital

Address

3-1-1 Asahi Matsumoto, Nagano-ken, Japan

Tel

+81-263-37-2572

Email

mdrinri@shinshu-u.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

Date of disclosure of the study information

2016

Year

07

Month

03

Day

URL releasing protocol

https://shinshu.bvits.com/rinri/Apply/show.aspx?TYPE=1&ID=7926

Publication of results

Published

URL related to results and publications

https://doi.org/10.1210/clinem/dgad144

Number of participants that the trial has enrolled

130

Results

The spironolactone group showed a significant reduction in UACR from baseline compared with the control group which showed an increased UACR (p = 0.0007, Wilcoxon rank-sum test and t-test). Although the spironolactone group had a statistically significant increase in serum potassium levels, none of the participants had a potassium level >5.5 mEq/L at 24 weeks. Further, participants with a higher initial serum potassium level tended to have a smaller increase (estimate -0.37, analysis of covariance).

Results date posted

2023

Year

05

Month

09

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

We enrolled 130 Japanese adults with type 2 diabetes and albuminuria (>30 mg/gCre) from July 2016 to December 2018 (84 from Shinshu University Medical Hospital, 31 from Takeda Internal Medicine Clinic, and 15 from Miyamoto Internal Medicine Clinic). The inclusion criteria were as follows: 1) aged >20 years, 2) estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m2 calculated using serum creatinine level, and 3) taking RAS blockers for over 180 days. The exclusion criteria were as follows: 1) serum potassium level > 5.0 mEq/L, 2) already taking MRAs, 3) history of adverse events caused by MRAs, and 4) pregnancy or breastfeeding.

Participant flow

In total, 130 patients were randomly assigned to two groups, with one receiving additive treatment with spironolactone (12.5 mg/day) and the other receiving medication therapy without spironolactone. Stratified randomization was performed at the Center for Clinical Research of Shinshu University Hospital. The stratifying factors for randomization were duration of diabetes (>10 years or <10 years), eGFR (>60 mL/min/1.73 m2 or <60 mL/min/1.73 m2), and urine albumin-to-creatinine ratio (UACR) (30 to 300 mg/gCre or >300 mg/gCre).
Follow-up visits were conducted at 12 weeks and 24 weeks of observational periods and 12 weeks after the end of the study. Blood pressure and body weight measurements, physical examinations, and interviews regarding adverse events were conducted at these visits. At each visit, we interviewed the participants about their urine color, food intake, whether they exercised hard, felt tired, had a cold, and were in their period because these factors could cause an increase in urinary albumin excretion. The primary and secondary endpoint data were obtained at the start of the study, 12-week, and 24-week observational periods. Urine and blood samples were collected at all times in the outpatient department. The criteria for decision-making if patients should discontinue the study were as follows: 1) eGFR <30 mL/min/1.73 m2, 2) serum potassium level >5.5 mEq/L, 3) systolic pressure <100 mmHg; and 4) gynecomastia with the wish of patients themselves to resign from the study.

Adverse events

One of the participants withdrew from the study because he became aware of gynecomastia. No other adverse events were observed.

Outcome measures

The primary outcome measure was the change in UACR from baseline to the 24-week intervention period. The secondary outcome measurements were the changes from baseline to the 24-week in serum potassium, serum creatinine, eGFR, cystatin C, uric acid, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, aldosterone, blood pressure, and body weight in the same intervention period.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2016

Year

06

Month

07

Day

Date of IRB

2016

Year

03

Month

14

Day

Anticipated trial start date

2016

Year

07

Month

01

Day

Last follow-up date

2019

Year

12

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2016

Year

07

Month

03

Day

Last modified on

2023

Year

05

Month

09

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026509