SGLT-2 Inhibition, Metabolomics and Cardiovascular/Kidney Disease

Type 2 Diabetes Mellitus Clinical Trial

Official title:

SGLT-2 Inhibition and Cardiovascular Disease. Metabolomics Study of Potential Factors Involved in Cardio- and Nephroprotection

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03919656
• Other study ID #: FIM-DAPA-2018-01
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 2019
• Est. completion date: April 2020

Study information

• Verified date: April 2019
• Source: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Contact: Jose Carlos Fernandez-Garcia, MD, PhD
• Phone: +34951034016
• Email: josecarlosfdezgarcia[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study evaluates the metabolomics changes associated with dapagliflozin treatment in patients with type 2 diabetes mellitus (T2DM). The participants in the study will be randomized to receive 10 mg dapagliflozin or placebo once daily for 12 weeks.

Description:

In this study, we hypothesize that metabolomics changes that occur in patients with T2DM after initiating SGLT2i (sodium-glucose cotransporter 2 inhibitors) treatment may be responsible for the beneficial cardiovascular and kidney effects observed in clinical trials with SGLT2i. Also, we propose that the study of the specific metabolome associated with the treatment with SGLT2i could help identify the possible metabolites and molecules that reduce CVD (cardiovascular disease) and renal disease in patients with T2DM.

The participants in the study will be randomized to receive 10 mg dapagliflozin or placebo once daily of for 12 weeks. Besides, all participants will be advised to engage in 150 min or more of moderate-to vigorous intensity physical activity per week, spread over at least 3 days/week, with no more than 2 consecutive days without activity and to engage in 2-3 sessions/week of resistance exercise on nonconsecutive days. Moreover, these patients will be advised to follow a lifestyle program that achieve a 500-750 kcal/day energy deficit or provide≈1,200-1,500 kcal/day for women and 1,500-1,800 kcal/day for men, adjusted for the individual's baseline body weight.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: April 2020
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age 18-75.

• BMI 27-39.9 kg/m2.

• T2DM on treatment with metformin and inadequate metabolic control (defined as HbA1c=6.5 -7%).

Exclusion Criteria:

• Pregnancy (all women of child-bearing age, unless on treatment with contraceptive methods, will undergo a pregnancy test)

• Breastfeeding

• Intolerance/allergy to dapagliflozin.

• Treatment with antidiabetic drug other than metformin.

• Impaired kidney function: Estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 (calculated using the CKD-EPI formula).

• Patients with established cardiovascular disease.

• Previous or current history of cancer of any kind.

• Uncontrolled hypertension (systolic blood pressure=160 mmHg or diastolic blood pressure=110 mmHg, despite adequate antihypertensive treatment).

• History of liver tumour or acute or chronic liver disease with impaired liver function: total bilirubin levels> 2.0 mg / dl or GOT/GPT levels three times higher than normal upper limit.

• Known HIV infection or active HBV or HCV infection.

• Other serious underlying diseases, which could affect the patient's ability to participate in the study.

• Reduced life expectancy (<12 months) due to advanced or terminal concomitant diseases.

In addition, female patients of child-bearing age will be advised to use contraceptive methods during the study period, given the contraindication of dapagliflozin and metformin during pregnancy as per normal clinical practice.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Dapagliflozin 10 mg
Dapagliflozin 10 mg daily in a green, plain, diamond shaped, film coated tablet (orally)
• Placebo Oral Tablet
Green, plain, diamond shaped, film coated tablet (orally). Does not contain active ingredient

Locations

Country	Name	City	State
Spain	Virgen de la Victoria University Hospital. Endocrinology Department	Malaga

Sponsors (1)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metabolomics changes in blood	Targeted and quantitative analysis by ultra-high-resolution liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ/MS). Analysis of specific families of metabolites selected from hypotheses generated by previous exploratory studies: changes in acylcarnitines and other intermediates of mitochondrial ß-oxidation and the urea cycle, branched-chain amino acids and biogenic amines	From baseline to week 12
Primary	Metabolomics changes in urine	Targeted and quantitative analysis by ultra-high-resolution liquid chromatography coupled to triple quadrupole mass spectrometry (UHPL-QqQ/MS). Analysis of specific families of metabolites selected from hypotheses generated by previous exploratory studies: changes in acylcarnitines and other intermediates of mitochondrial ß-oxidation and the urea cycle, branched-chain amino acids and biogenic amines	From baseline to week 12
Secondary	BMI (body mass index) changes	Measured by body composition analysis	From baseline to to week 12
Secondary	Changes in insulin resistance	Measured as HOMA-IR (homeostatic model assessment of insulin resistance)	From baseline to to week 12
Secondary	Changes in metabolic control	Measured as HbA1c (glycated hemoglobin)	From baseline to to week 12
Secondary	Changes in Quality of Life: 36-Item Short Form Health Survey (SF-36) questionnaire	The SF-36 has eight scaled scores: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. The scores are weighted sums of the questions in each section. Scores range from 0 - 100, lower scores indicate more disability, and higher scores indicate less disability	From baseline to to week 12
Secondary	Changes in albuminuria	Modifications in albuminuria, measured as albumin excretion rate (AER)	From baseline to to week 12