Clinical trial NCT05033054: Effect of SGLT2i on Cardiovascular Biomarkers in Patients with Type 2 Diabetes and CKD Stage 3b-4
Official title: Effect of SGLT2i on Cardiovascular Biomarkers in Patients with Type 2 Diabetes and CKD Stage 3b-4
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Kidney Disease, Chronic
Diabetes
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2021-09-02
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient with type 2 diabetes mellitus and stage 3b-4 chronic kidney disease.

Brief summary: This is a prospective, observational study to assess the effect of SGLT2 inhibitors on surrogate markers of kidney and cardiovascular health in patients with stage 3b and 4 chronic kidney disease (CKD).

This study includes three clinic in person visits and weekly telephone visits for 12 weeks.

1. Recruit 28 patients with CKD stages 3b-4 and follow up for 12 weeks
2. Determine the effect of interventions on the primary outcome variable serum klotho measured by immunoprecipitation-immunoblot


Eligibility criteria: Inclusion Criteria:

* 18-80 years of age
* All races and ethnicities
* All genders
* Type 2 diabetes mellitus
* History of hypertension defined as \> 130 or \> 80 mmHg or normotensive on pharmacologic therapy
* Estimated glomerular filtration rate (GFR) (CKD Epi equation) of 15-44 ml/min/1.73 m2 (Stages 3b-4 CKD)
* Urinary albumin creatinine ratio of \> 200 mg/g \<5000mg/g
* Ability of study participant or legally authorized representative to provide informed written consent
* Able to maintain stable dose of any vitamin D and any calcium supplements for 180 days post randomization.

Exclusion Criteria:

* Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis or anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
* Receiving cytotoxic therapy, immunosuppressive therapy or other immunotherapy for primary or secondary renal disease within 6 months prior to enrolment
* History of organ transplantation
* Receiving therapy with a sodium glucose co-transporter 2 (SGLT2) inhibitor within 8 weeks prior to enrolment or previous intolerance of an SGLT2 inhibitor
* Type 1 diabetes (T1D)
* Active use of SGLT2 inhibitor
* History of persistent hypercalcemia (serum total Calcium \> 10.5 mg/dl)
* Body mass index \> 45 kg/m2
* Active on kidney transplant list
* Inability to provide informed consent
* Any condition outside the renal and cardiovascular disease area, such as but not limited to malignancy, with a life expectancy of less than 2 years based on investigator´s clinical judgement
* Active malignancy requiring treatment at the time of screening (with the exception of successfully treated basal cell or treated squamous cell carcinoma).
* Hepatic impairment (aspartate transaminase \[AST\] or alanine transaminase \[ALT\] \>3x the upper limit of normal \[ULN\]; or total bilirubin \>2x ULN at time of enrolment)
* Women of child-bearing potential (ie, those who are not chemically or surgically sterilized or who are not post-menopausal) who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator or women who have a positive pregnancy test at enrolment or randomization or women who are breast-feeding
* Participation in another clinical study with an investigational product (IP) during the last month prior to Enrolment
* Inability of the patient, in the opinion of the investigator, to understand and/or comply with procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study. Patients who cannot complete the patient reported outcome (PRO) assessments can still participate in the study

Primary outcomes:
measure: Change in serum klotho levels at 6 weeks
timeFrame: Baseline, 6 weeks
measure: Change in serum klotho levels at 12 week
timeFrame: Baseline, 12 weeks
Secondary outcomes:
measure: Change in serum magnesium levels at 6 weeks
timeFrame: Baseline, 6 weeks
measure: Change in serum magnesium levels at 12 weeks
timeFrame: Baseline, 12 weeks
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Robert Toto, MD
role: PRINCIPAL_INVESTIGATOR
References: