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Study to Develop a Kinetic Model for FDG and Me4FDG in Kidneys of Type 2 Diabetic Patients

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ClinicalTrials.gov Identifier: NCT03557138
Recruitment Status : Recruiting
First Posted : June 14, 2018
Last Update Posted : December 12, 2019
Sponsor:
Information provided by (Responsible Party):
Univ.-Prof. Dr. Marcus Hacker, Medical University of Vienna

Brief Summary:
In this study, using 18F-FDG and Gd-DTPA PET/MRI, we are aiming to perform a dynamic PET/MRI imaging using 18F-FDG and Me4FDG for a group of type 2 diabetic patients scheduled for Glifozine therapy due to the bad metabolic control to assess changes in renal function before and 1 to 2 weeks after initiating therapy with Gliflozine. Furthermore we aim to study the temporal behavior of 18F-FDG and Me4FDG activity in certain kidney regions of the diabetic participants to estimate basic kidney parameters using time activity curve. Further, we intend to find a kinetic model that describes the behavior of glucose in each part of the kidney can be acquired mathematically and to find out whether conclusions about the glucose reabsorption capability of the kidney in diabetes can be achieved in general. In addition, we aim to simultaneously determine renal lesions as well as obstructions with the fused, high definition, and three dimensional images of the kidney and estimate kidney function parameters from the dynamic Gd-DTPA MRI scan and compare them to the kidney function determined with the kinetic model.

Condition or disease Intervention/treatment Phase
Type2 Diabetes Mellitus Behavioral: alpha-Methyl-4-deoxy-4-[(18)F]fluoro-D-glucopyranoside Not Applicable

Detailed Description:
Independent of insulin, inhibition of sodium-glucose transporter 2 (SGLT2) in the proximal tubular cells prevents glucose reabsorption and promotes glucose excretion by causing glycosuria. Therefore, SGLT2 inhibitors known as Gliflozine are recently authorized for the treatment of type 2 diabetes mellitus (DM), whether as monotherapy or in combination with other anti-diabetic medications including insulin. To our knowledge, there is still no established kinetic model that describes precisely the reabsorption mechanism of glucose in the proximal tubules and that shows the impact of Gliflozine on renal function in diabetic patients. Therefore, the temporal behavior of glucose in the various kidney regions needs to be studied. Currently, the most promising tool is a combined positron emission tomography and magnetic resonance imaging (PET/MRI) using radioactive glucose analog 2-deoxy-2-(18F)fluoro-D-glucose (FDG). The MRI scan in combination with the kidney-specific gadolinium based contrast agent diethylenetriaminepentacetate (Gd-DTPA) images the organ with high resolution allowing an estimation of kidney parameters; the PET scan on the other hand shows the dynamic behavior of the glucose analog FDG. However, the reabsorption process of FDG in the kidney is controversial. For this reason, a dynamic PET/MRI image using 18F-FDG will be performed for diabetic patients, need the Gliflozine therapy, directly before and 1 to 2 weeks after therapy initiation. We aim, generally, to study the chronological behavior 18F-FDG activity in kidneys and to show, particularly, the reabsorption process under the influence of SGLT2 inhibition. Furthermore, conclusions about the glucose reabsorption capability of the kidney in these patients might be achieved and a kinetic model that describes the exact behavior of glucose in each part of the kidney can be mathematically acquired. We aim, additionally, to compare the PET/MRI images with the levels of diabetic metabolic control before and 1 to 2 weeks after initiating therapy with Gliflozine to show whether conclusions about therapy response can be drawn with FDG among the participants which arises from a broader peak in case of medication. A possible explanation is that the Patlak slope is among other influenced by the re-absorption process: if re-absorption is lowered due to the medication, the peak gets broader leading to a lower Patlak slope. We therefore conclude that reabsorption might be studied with FDG. Furthermore, a first draft of a kinetic model could be developed with the collected data According to this model, the re-absorption is mainly covered by the rate-constant k3. However, there was no correlation found between k3 and the above mentioned Patlak slope which most likely is a measure for re-absorption. Furthermore, the fit algorithm not always leads to meaningful results. This leads to the assumption that the model is not yet finished and further input data are needed. The model allows calculating the TACs of the visible renal sub-regions (Cortex, Medulla and Pelvis). In comparison with the measured TACs, the calculated ones deliver similar shapes. Although it seems from these results promising to study diabetes type II with a routine tracer like FDG, the kinetic model is hampered by the low affinity of FDG for the SGL transporter, which makes a quantification difficult. Therefore, an alternative radiopharmaceutical shall be applied which is similar to FDG but mainly re-abosrbed via SGLT: alpha-Methyl-4-[18F]FDG (Me4FDG).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Study to Develop a Kinetic Model for FDG and Me4FDG in Kidneys of Type 2 Diabetic Patients With SGLT2 Inhibitor Therapies
Actual Study Start Date : February 22, 2017
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Me4FDG
Intravenous injection of alpha-Methyl-4-deoxy-4-[(18)F]fluoro-D-glucopyranoside (Me4FDG) and FDG for evaluation the kidney kinetic model of FDG and Me4FDG in type 2 diabetic patients with SGLT2-inhibitor therapies.
Behavioral: alpha-Methyl-4-deoxy-4-[(18)F]fluoro-D-glucopyranoside
positron emission tomography and magnetic resonance imaging (PET/MRI) of kidneys of diabetic patients using alpha-Methyl-4-deoxy-4-[(18)F]fluoro-D-glucopyranoside (Me4FDG)




Primary Outcome Measures :
  1. Kinetic behavior of glucose reabsorption [ Time Frame: one year ]
    mathematically acquire a kinetic model of glucose reabsorption capability in each part of the kidney in type 2 diabetic patient under SGLT2-inhibitor therapies.


Secondary Outcome Measures :
  1. positron emission tomography (PET) [ Time Frame: one year ]
    Assess basic kidney parameters using time activity curve



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   male and female diabetic patients with SGLT2-inhibitor therapies
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Type 2 DM.
  • Aged 20 -74 years.
  • HbA1c level > 7%.
  • Planned initiation of Gliflozine treatment.
  • Intact renal function (serum creatinine < 1.5mg/dl or urinary albumin:creatinine ratio < 300mg/g in random urine sample).
  • Written informed consent.

Exclusion Criteria:

  • Age < 18 years, as kidneys may not be fully developed and not working properly yet.
  • Impaired renal function (serum creatinine ≥ 1.5mg/dl or urinary albumin:creatinine ratio > 300mg/g in random urine sample) as well as anatomically altered or harmed kidneys could falsify the results due to their different or high alterable time activity curves.
  • Patients under corticosteroids and diuretics therapies.
  • MR-unsafe implants such as pacemakers and implantable cardioverter-defibrillators
  • Intolerance of MRI contrast agents.
  • Claustrophobia.
  • Patients, who are not able to lie still without changing position for a minimum of 30 minutes.
  • Pregnancy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03557138


Contacts
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Contact: Marcus Hacker, Prof., MD +43 14040055310 marcus.hacker@meduniwien.ac.at
Contact: Sazan Rasul, MD, PHD +43 14040055480 sazan.rasul@meduniwien.ac.at

Locations
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Austria
Medical University of Vienna, Department of Radiology and Nuklear Medicine Recruiting
Vienna, Austria, 1090
Contact: Marcus Hacker, Prof., MD       marcus.hacker@meduniwien.ac.at   
Principal Investigator: Marcus Hacker, Prof., MD         
Sub-Investigator: Sazan Rasul, MD, PhD         
Sub-Investigator: Barbara Geist, Dr., Msc.         
Sponsors and Collaborators
Medical University of Vienna
Investigators
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Principal Investigator: Marcus Hacker, Prof., MD Medical University of Vienna

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Univ.-Prof. Dr. Marcus Hacker, Professor, MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT03557138    
Other Study ID Numbers: 1128/2016
First Posted: June 14, 2018    Key Record Dates
Last Update Posted: December 12, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Univ.-Prof. Dr. Marcus Hacker, Medical University of Vienna:
SGLT2 inhibitor
18F-FDG
alpha-Methyl-4-18F-FDG
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs