Clinical trial NCT04004793: Remission of Type 2 Diabetes With Dapagliflozin (READ Trial)
Official title: Effect of Dapagliflozin for Remission of Type 2 Diabetes Mellitus: A Multicenter, Randomized, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
First posted: 2019-07-02
Enrollment: 328
Sex: ALL
Minimum age (years): 20
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, double-blind, placebo-controlled study to assess the effect of dapagliflozin add-on intensive lifestyle intervention for remission of type 2 diabetes in obese patients with Type 2 Diabetes Mellitus. The study consists of a 12-months treatment period (in which they will receive either Dapagliflozin plus intensive lifestyle intervention or placebo plus intensive lifestyle intervention in addition to the background therapy), and a 2-month follow-up period after treatment period.

Detailed description: Diabetes remission is an important issue which has not been well studied. Some studies showed that bariatric surgery and intensive lifestyle intervention could lead to remission in diabetic patients. Our present study aims to assess the effect of dapagliflozin add-on intensive lifestyle intervention on remission of type 2 diabetes in obese patients with type 2 diabetes. This is a multicenter, randomized, double-blind, placebo-controlled study. The study consists of a 12-months treatment period (in which subjects will receive either dapagliflozin plus intensive lifestyle intervention or placebo plus intensive lifestyle intervention in addition to the background therapy), and a 2-month follow-up period after treatment period.

Eligibility criteria: Inclusion Criteria:

* Men or women aged 20-70 years old who had a BMI ≥25 kg/m2.
* Subjects had been diagnosed with type 2 diabetes within 6 years
* HbA1C ≥6.5% and ≤10.0% at screening if on treatment with metformin alone or without antidiabetic agents, or HbA1C \<6.5% at screening if on metformin treatment alone
* Able and willing to provide written informed consent and to comply with the study

Exclusion Criteria:

1. Patients have a history of myocardial infarction, unstable angina, cardiac surgery or revascularization (coronary artery bypass graft/percutaneous transluminal coronary angioplasty), or congestive heart failure New York Heart Association Class III or IV.
2. Current insulin use.
3. Weight loss of more than 5kg within the past 6 months.
4. Women who are pregnant or plan to become pregnant.
5. Diagnosis or history of acute metabolic diabetic complications such as ketoacidosis or hyperglycemic hyperosmolar state, or diabetes insipidus within 30 days.
6. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake.
7. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participating in another trial (involving an investigational drug and /or follow-up).
8. Patients with clinically apparent hepatobiliary disease, including but not limited to chronic active hepatitis and/or severe hepatic insufficiency. ALT or AST \> 3x upper limit of normal (ULN), or serum total bilirubin (TB) \>34.2 μmol/L (\>2 mg/dL).
9. Patients with severe renal impairment or end-stage renal disease (eGFR\< 45 mL/min/1.73 m2).
10. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
11. Malignancy within 5 years of the enrollment visit.
12. Known immunocompromised status, including but not limited to, individuals who had undergone organ transplantation or acquired immunodeficiency syndrome (AIDS).
13. History of bone fracture secondary to diagnosed severe osteoporosis.
14. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM.
15. Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, or phendimetrazine within 30 days of enrollment visit.
16. Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anaemia).
17. Administration of any other investigational drug within 30 days of planned enrollment to this study, or within 5 half-life periods of other investigational drugs.
18. Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or has any severe concurrent medical or psychological condition that may affect the interpretation of efficacy or safety data

Primary outcomes:
measure: Incidence of patients with diabetes remission
timeFrame: During the 12-month intervention
Secondary outcomes:
measure: Proportion of patients with diabetes remission
timeFrame: during the 12-month intervention
measure: Net change in body weight
timeFrame: during both 12 and 14 months
measure: Net change in waist circumference
timeFrame: during both 12 and 14 months
measure: Net change in HOMA-IR
timeFrame: during both 12 and 14 months
measure: Net change in serum lipids
timeFrame: during both 12 and 14 months
measure: Net change in HbA1c
timeFrame: during both 12 and 14 months
measure: Net change in body fat
timeFrame: during both 12 and 14 months
measure: Net change in SBP
timeFrame: during both 12 and 14 months
measure: Net change in Serum Creatine
timeFrame: during both 12 and 14 months
measure: Net change in Albuminuria
timeFrame: during both 12 and 14 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Medical college of
Study officials:
affiliation: Fudan University
name: Xiaoying Li, MD
role: PRINCIPAL_INVESTIGATOR
References: