PROTOCOL 3: Role of the Renal Nerves in the Increase in EGP in Response to Glucosuria

NCT03168295 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: HSC20160042HR01DK107680
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose/Objectives: Examining the effect of SGLT2 inhibition on EGP and plasma glucose concentration in diabetic and non-diabetic subjects after kidney transplantation (i.e. renal denervation) or in subjects after renal sympathectomy (63) can add insight about the possible role of a neural arc which mediates the changes in plasma glucagon and/or insulin concentration in response to glucosuria.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Change in Endogenous Glucose Production (EGP)

  Renal transplant subjects with native kidneys intact underwent measurement of EGP with an 8 hour infusion of 3-3H-glucose on 2 separate days with the administration in random order of either dapagliflozin 10mg or placebo after 3 hours of the tracer equilibration period. The equilibration at 3 hours was considered the baseline measurement. Measurement of change in endogenous glucose production was obtained for all subjects.

  baseline and 240-300 minutes

Secondary Outcomes (2)

• Change in Fasting Plasma Glucose

  baseline and 240-300 minutes

• Change in Fasting Plasma Insulin

  baseline and 240-300 minutes

Study Arms (3)

Placebo first and then dapagliflozin

EXPERIMENTAL

Renal transplant subjects with intact native kidneys with Type 2 Diabetes Mellitus receive dapagliflozin then placebo

Drug: Dapagliflozin 10mg then Placebo Oral Tablet; Drug: Placebo Oral Tablet then Dapagliflozin 10mg

Dapagliflozin first then placebo

ACTIVE COMPARATOR

Renal transplant subjects with intact native kidneys who are non-diabetic receive placebo then dapagliflozin

Drug: Dapagliflozin 10mg then Placebo Oral Tablet; Drug: Placebo Oral Tablet then Dapagliflozin 10mg

Control Group

OTHER

Subjects who are type 2 diabetes mellitus who have not undergone renal transplant.

Drug: Dapagliflozin 10mg then Placebo Oral Tablet

Interventions

Dapagliflozin 10mg then Placebo Oral Tablet DRUG

SGLT2 inhibitor - Dapagliflozin then Placebo

Also known as: Farxiga then placebo

Control Group; Dapagliflozin first then placebo; Placebo first and then dapagliflozin

Placebo Oral Tablet then Dapagliflozin 10mg DRUG

Placebo then SGLT2 inhibitor - Dapagliflozin

Also known as: Placebo then Farxiga

Dapagliflozin first then placebo; Placebo first and then dapagliflozin

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age = 18-70 years
• BMI = 18.5-40 kg/m2
• HbA1c ≥ 7.0% and ≤10.0% for type 2 diabetics
• males or females
• Must be at least 3 months post renal transplantation and be on a stable dose of prednisone (≤5 mg/day), tacrolimus, and mycophenolate mofetil
• Not taking any antidiabetic medications or who are treated with metformin, sulfonylurea, dipeptidyl peptidase 4 (DPP4) inhibitor, thiazolidinedione or some combination
• Must be in good general health as determined by physical exam, medical history, blood chemistries, CBC, TSH, T4, EKG and urinanalysis

You may not qualify if:

• Subjects who are taking insulin or SGLT2 inhibitor are excluded
• Only subjects whose body weight has not been stable (± 3 lbs) over the preceding three months and/or who participate in an excessively heavy exercise program will be excluded.
• Individuals with evidence of proliferative diabetic retinopathy, plasma creatinine \>1.4 females or \>1.5 males (and eGFR \<45ml/min.1.73m2), or 24-hour urine albumin excretion \> 300 mg will be excluded.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Related Publications (2)

• Daniele G, Solis-Herrera C, Dardano A, Mari A, Tura A, Giusti L, Kurumthodathu JJ, Campi B, Saba A, Bianchi AM, Tregnaghi C, Egidi MF, Abdul-Ghani M, DeFronzo R, Del Prato S. Increase in endogenous glucose production with SGLT2 inhibition is attenuated in individuals who underwent kidney transplantation and bilateral native nephrectomy. Diabetologia. 2020 Nov;63(11):2423-2433. doi: 10.1007/s00125-020-05254-w. Epub 2020 Aug 22.

  PMID: 32827269 DERIVED

• Solis-Herrera C, Daniele G, Alatrach M, Agyin C, Triplitt C, Adams J, Patel R, Gastaldelli A, Honka H, Chen X, Abdul-Ghani M, Cersosimo E, Del Prato S, DeFronzo R. Increase in Endogenous Glucose Production With SGLT2 Inhibition Is Unchanged by Renal Denervation and Correlates Strongly With the Increase in Urinary Glucose Excretion. Diabetes Care. 2020 May;43(5):1065-1069. doi: 10.2337/dc19-2177. Epub 2020 Mar 6.

  PMID: 32144165 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Carolina Solis-Herrera
• Organization: University of Texas Health San Antonio

solisherrera@uthscsa.edu

(210) 567-6691

Study Officials

• Ralph A DeFronzo, MD

  The University of Texas Health Science at San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Post renal transplant type 2 diabetes mellitus patients and non-diabetic mellitus patients after renal transplant with a control group of type 2 diabetes mellitus who have not undergone renal transplant

Study Record Dates

• First Submitted: May 24, 2017
• First Posted: May 30, 2017
• Study Start: October 1, 2016
• Primary Completion: October 1, 2018
• Study Completion: May 15, 2019
• Last Updated: September 17, 2020
• Results First Posted: January 14, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)