Tofogliflozin mechanism of Action to Retain cardiac function evaluated by (123)I-MIBG scintigraphy, Echocardiography and biomarkers in T2DM patients with Heart Failure

JRCT ID: jRCTs041210022

Registered date:18/05/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Type 2 diabetes mellitus with Heart failure
• Date of first enrollment: 18/05/2021
• Target sample size: 50
• Study type: Interventional
• Intervention(s): Tofogliflozin at a dose of 20 mg orally once daily before or after breakfast for 24 weeks.

Outcome(s)

Primary Outcome

Changes in the following indicators of I-123 MIBG scintigraphy at 24 weeks after administration of tofogliflozin from baseline (comparison before and after administration)
Late H / M ratio

Secondary Outcome

Important secondary evaluation items
Change in the following indicators of I-123 MIBG scintigraphy at 24 weeks after administration of tofogliflozin from baseline (comparison before and after administration)Change of following parameters
(Time frame:0 to 24 weeks, before and after)
WR (washout rate)
Early H / M ratio

Secondary evaluation item
Amount of change in various indicators from baseline to 24 weeks after administration of tofogliflozin
(comparison before and after administration, rate of change for lipid system)
Correlation between the amount of change in various indicators (rate of change for lipid system) at 24 weeks after administration of tofogliflozin frombaseline
<Parameters>
Vital:height, weight, BMI, body composition (body fat mass, body fat percentage, lean body mass,muscle mass, body water content, basal metabolicrate), blood pressure (SBP / DBP), heart rate electrocardiogram parameters, chest radiographic finding
Echocardiography:GLS, LV end-diastolic diameter,
LV end-systolic diameter,LA volume, LV volume, LV mass, DcT, LVEF, E / A, e, E / e, E wave, A wave, TRPG, IVC diameter, right atrial pressure (estimated)
Carbohydrate system:HbA1c, fasting blood glucose, fasting insulin, HOMA-IR, pancreatic glucagon, active GLP-1, active GIP
Lipid system:TC, LDL-C (calculation formula), LDLC(direct method), TG, HDL-C, Lp (a), sdLDL, ApoB, ApoA1, ApoA2
Blood system:WBC,RBC,Platelets,Ht,Hb,MCV (calculation formula), MCH (calculation formula), MCHC (calculation formula),EPO,troponinT
Kidney system:eGFR,serum creatinine,Urine albumin / creatinine ratio,UA,BUN,urinary NGAL
Liver system:AST,ALT,ALP,gamma-GTP
Others:total ketone body, ketone body fraction,hsCRP,8-OHdG, aldosterone / renin activity ratio, dopamine, noradrenaline, adrenaline, NT-proBNP, adiponectin, stem cells (CD34 positive cells)
safety:number and rate of adverse events, number and rate of diseases

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1.Aged >=20 years
2.Diagnosis of type 2 diabetes mellitus and HbA1c of >= 6.5% and =< 10.0%* within 12 weeks before informed consent
*If taking medication for type 2 diabetes since before informed consent,patients whose research physicians determined needed additional type 2 diabetes mellitus drugs were not affected by HbA1c levels.
3.Established documented diagnosis of chronic heart failure NYHA class 2 or 3, for at least 8 weeks prior to informed consent
4.LVEF < 40% within 12 weeks prior to informed consent
5.Sinus rhythm and NT-proBNP >= 125 pg/mL or patients with atrial fibrillation and NT-proBNP >= 365 pg/mL within 12 weeks prior to informed consent
6.eGFR >= 30mL/min/1.73m^2 within 12 weeks prior to informedconsent
7.Signed and dated informed consent

Exclude criteria

1.Receiving therapy with a SGLT2 inhibitor within 8 weeks prior to informed consent
2.Receiving therapy with an insulin within 8 weeks prior to informed consent
3.Change in drugs or dosage within 4 weeks prior to informed consent
4.Sympomatic hypotension or systolic blood pressure < 95mmHg
5.History of hospitalization for acute heart failure or heart failure within 4 weeks prior to informed consent
6.History of myocardial infarction, unstable angina, stroke or transient ischemic attack within 12 weeks prior to informed consent
7.History of PCI, CABG, valvular repair/replacement within 12 weeks prior to informed consent or with plans
8.History of Pacemaker implantation within 12 weeks prior to informed consent or plans
9.Previous cardiac transplantation or with plans
10.Restrictive cardiomyopathy, active myocarditis, constrictive pericarditis, hypertrophic cardiomyopathy or valvular disease
11.Symptomatic bradycardia
12.Known hypersensitivity to iodine hypersensitivity
13.Receiving therapy with Reserpine,Tricyclic Antidepressants,labetalol
14.Parkinsons disease
15.Malignant tumor in need of treatment
16.Indication of liver disease, defined by serum levels of either ALT, AST above 3 times upper limit of normal, or total bilirubin above 2 times upper limit of normal
17.Severe impaired renal function, defined as eGFR < 30 mL/min/1.73m^2
18.BMI < 18.5 kg/m^2
19.Breastfeeding, pregnant or intent to be pregnant
20.Severe ketosis, diabetic coma or precoma
21.Severe infection, preioperative or serious trauma
22.Known hypersensitivity to tofogliflozin
23.Inappropriate condition for this clinical trial based on the investigators clinical judgement

Related Information

• Primary Sponsor: Murohara Toyoaki
• Source(s) of Monetary Support: Kowa Company, Ltd.