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

December 11, 2019 updated by: Univ.-Prof. Dr. Marcus Hacker, Medical University of Vienna

Study to Develop a Kinetic Model for FDG and Me4FDG in Kidneys of Type 2 Diabetic Patients With SGLT2 Inhibitor Therapies

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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).

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
20

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Recruiting
        • Medical University of Vienna, Department of Radiology and Nuklear Medicine
        • Contact:
        • Principal Investigator:
          • Marcus Hacker, Prof., MD
        • Sub-Investigator:
          • Sazan Rasul, MD, PhD
        • Sub-Investigator:
          • Barbara Geist, Dr., Msc.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 74 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: DIAGNOSTIC
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
one year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
positron emission tomography (PET)
Time Frame: one year
Assess basic kidney parameters using time activity curve
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Medical University of Vienna

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Marcus Hacker, Prof., MD, Medical University of Vienna

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 22, 2017

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 4, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 13, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 14, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 12, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 11, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 1128/2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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