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Reduction of Peritoneal Glucose Uptake With Use of SGLT2 in Humans Undergoing Peritoneal Dialysis Treatment (PRESERVE)

Primary Purpose

End Stage Renal Disease, Peritoneal Dialysis Complication

Status
Enrolling by invitation
Phase
Phase 2
Locations
Denmark
Study Type
Interventional
Intervention
Dapagliflozin 10 MG [Farxiga]
Sponsored by
Holbaek Sygehus
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End Stage Renal Disease focused on measuring SGLT2-inhibition, dapagliflozin

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Written informed consent
  2. Age above 18 years of age
  3. In stable peritoneal dialysis for more than 14 days.

Exclusion Criteria:

  1. In treatment with SGLT2i currently or within the last 90 days.
  2. Treatment for peritoneal infection within the last 30 days.
  3. Any hospitalization within the last 30 days.
  4. Anaphylaxis to the IMP.
  5. Impaired lever function with ALAT above normal range within the last 6 month.
  6. Sever efflux problems during peritoneal dialysis for the last 14 days, judged by the investigator.
  7. Non-menopausal defined as menstruation within the last 12 month without any other medical cause. Only applicable for female participants.
  8. Substance abuse, judged by the investigator.
  9. Incapable to follow study protocol, judged by the investigator.
  10. Previously included in this clinical trial and exposed to the IMP.
  11. Included in another clinical trial with exposure to any IMP within the last 30 days.

Sites / Locations

  • University Hospital Copenhagen - Holbaek

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

On treatment

Arm Description

Assigned to oral treatment with dapagliflozin 10 mg for three consecutive days.

Outcomes

Primary Outcome Measures

Peritoneal glucose uptake (mg/ dL)
Glucose level in peritoneal fluid during a four hour standardized peritoneal dialysis. Change in total glucose uptake before and after treatment (treatment periode of three days)

Secondary Outcome Measures

Fluid volume (ml)
Fluid volume ultra-filtrated during peritoneal dialysis.
Plasma glucose level (mg/ dL)
Glucose levels in blood and peritoneal-fluid during peritoneal dialysis. Comparaison of maximal plasma level.
Pharmacokinetics (nmol)
Dapagliflozin and its metabolites levels in blood and peritoneal-fluid
Adverse events (events)
Safety in terms of AE and/or SAE

Full Information

First Posted
January 13, 2022
Last Updated
February 11, 2022
Sponsor
Holbaek Sygehus
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1. Study Identification

Unique Protocol Identification Number
NCT05250752
Brief Title
Reduction of Peritoneal Glucose Uptake With Use of SGLT2 in Humans Undergoing Peritoneal Dialysis Treatment
Acronym
PRESERVE
Official Title
Reduction of Peritoneal Glucose Uptake With Use of SGLT2 in Humans Undergoing Peritoneal Dialysis Treatment. A Proof of Concept Phase 2a Clinical Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Enrolling by invitation
Study Start Date
November 18, 2021 (Actual)
Primary Completion Date
February 27, 2022 (Anticipated)
Study Completion Date
December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Holbaek Sygehus

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
End stage renal disease is annually diagnosed in about one thousand patients in Denmark, and one of the treatment modalities in renal replacement therapy is peritoneal dialysis with about 25 % of patients assigned to this treatment (Hommel2010). Peritoneal dialysis is based on the principle of filtering waste products to peritoneal fluid and by exchange of peritoneal fluid eliminate waste products from the body. In peritoneal dialysis commonly used fluids contain glucose. Exposure to high glucose levels in peritoneal fluid during peritoneal dialysis has several side effects. Primarily, as glucose passes over and into the peritoneal membrane it causes local inflammation which leads to fibrosis over time (Zhou2016). Fibrosis limits the capacity of the exchange of water and waste products over the peritoneal membrane. The decrease of peritoneal exchange capacity is most commonly the reason for termination of peritoneal dialysis. SGLT2-channels are identified in peritoneal mesothelial cells of rats (Debray-Carcia 2016), and most recently also in humans (Shentu2021). An in vitro model of human peritoneal mesothelial cells incubated with the SGLT2-inhibitor (empagliflozin) has shown significantly decrease in glucose uptake (Zhou2019). Exposure to intraperitoneal empagliflozin in rats, reduced the uptake of glucose over the peritoneal membrane significantly by 78 % and the ultrafiltration was increased (Zhou2019). Currently, to our knowledge, no clinical trials have been conducted in humans attending peritoneal dialysis with the aim of investigating either the effect or safety of SGLT2i, as it is indeed the first of its kind, with the aim of including participants in peritoneal dialysis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End Stage Renal Disease, Peritoneal Dialysis Complication
Keywords
SGLT2-inhibition, dapagliflozin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Cross-over. Off-On-Off treatment. Dose response
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
On treatment
Arm Type
Other
Arm Description
Assigned to oral treatment with dapagliflozin 10 mg for three consecutive days.
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10 MG [Farxiga]
Intervention Description
Primary end-points are measure before (day 0), on treatment (day 1 and day 3) and after treatment (day 21)
Primary Outcome Measure Information:
Title
Peritoneal glucose uptake (mg/ dL)
Description
Glucose level in peritoneal fluid during a four hour standardized peritoneal dialysis. Change in total glucose uptake before and after treatment (treatment periode of three days)
Time Frame
Day 0 (baseline), Day 3 (max dose of treatment)
Secondary Outcome Measure Information:
Title
Fluid volume (ml)
Description
Fluid volume ultra-filtrated during peritoneal dialysis.
Time Frame
Measured at end of each peritoneal dialysis. Peritoneal dialysis done af Day 0, Day 1 (first day of treatment) and day 3 (max dose of treatment)
Title
Plasma glucose level (mg/ dL)
Description
Glucose levels in blood and peritoneal-fluid during peritoneal dialysis. Comparaison of maximal plasma level.
Time Frame
Measured at end of each peritoneal dialysis. Peritoneal dialysis done af Day 0, Day 1 (first day of treatment) and day 3 (max dose of treatment).
Title
Pharmacokinetics (nmol)
Description
Dapagliflozin and its metabolites levels in blood and peritoneal-fluid
Time Frame
Samples for biobank - samples drawn at end of each peritoneal dialysis. Peritoneal dialysis done af Day 0, Day 1 (first day of treatment) and day 3 (max dose of treatment). Samples are drawn every 30 minuttes during each peritoneal dialysis.
Title
Adverse events (events)
Description
Safety in terms of AE and/or SAE
Time Frame
At day 1 (first day of treatment), day 3 (max dose of treatment) and day 30 (four weeks after treatment)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent Age above 18 years of age In stable peritoneal dialysis for more than 14 days. Exclusion Criteria: In treatment with SGLT2i currently or within the last 90 days. Treatment for peritoneal infection within the last 30 days. Any hospitalization within the last 30 days. Anaphylaxis to the IMP. Impaired lever function with ALAT above normal range within the last 6 month. Sever efflux problems during peritoneal dialysis for the last 14 days, judged by the investigator. Non-menopausal defined as menstruation within the last 12 month without any other medical cause. Only applicable for female participants. Substance abuse, judged by the investigator. Incapable to follow study protocol, judged by the investigator. Previously included in this clinical trial and exposed to the IMP. Included in another clinical trial with exposure to any IMP within the last 30 days.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morten Lindhardt, MD, PhD
Organizational Affiliation
Copenhagen University Hospital - Holbaek
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Copenhagen - Holbaek
City
Holbæk
State/Province
Zealand
ZIP/Postal Code
4300
Country
Denmark

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The data material used in this study are available from the corresponding author on reasonable request which will not conflict with the anonymity and confidentiality of the data.
IPD Sharing Time Frame
Depended on the request - Days to weeks
IPD Sharing Access Criteria
Not conflict with the anonymity and confidentiality of the data and a signed contract for data sharing.

Learn more about this trial

Reduction of Peritoneal Glucose Uptake With Use of SGLT2 in Humans Undergoing Peritoneal Dialysis Treatment

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