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TreatIng Microalbuminuria Over 24 Weeks in Subjects With or Without Type 2 Diabetes or HYpertension (TIMOTHY)

Primary Purpose

Albuminuria

Status
Terminated
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
Dapagliflozin 10Mg Tab
Placebo
Sponsored by
Hiddo Lambers Heerspink
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Albuminuria

Eligibility Criteria

45 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 45 to 80 years
  • Persistent urinary albumin:creatinine ratio (UACR) ≥ 2.5 mg/mmol (~25 mg/g)
  • Willing to sign informed consent

Exclusion Criteria:

Diagnosis of type 1 diabetes mellitus

  • eGFR < 25 ml/min/1.73m2
  • UACR > 3500 mg/g
  • Concurrent treatment with SGLT2 inhibitor
  • Receiving immunosuppressive therapy within 6 months prior to enrolment
  • History of diabetic ketoacidosis
  • Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin.
  • Initiation or changes in the dose of interventions in the renin-angiotensinaldosterone- system, diuretics, GLP-1 receptor agonists within 6 weeks of screening will not be allowed.

  • Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following:

    • History of active inflammatory bowel disease within the last six months;
    • Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
    • Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months;
    • Pancreatic injury or pancreatitis within the last six months;
    • Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at the screening visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt;
    • Evidence of urinary obstruction or difficulty in voiding at screening
  • History of severe hypersensitivity or contraindications to dapagliflozin
  • Subjects who, in the assessment of the investigator, may be at risk for dehydration or volume depletion that may affect the interpretation of efficacy or safety data
  • Participation in any clinical intervention study within 3 months prior to initial dosing.
  • History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening.
  • History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
  • Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
  • Pregnancy or breastfeeding

Sites / Locations

  • UMCG

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Dapagliflozin 10mg/day

Arm Description

Outcomes

Primary Outcome Measures

urinary albumin/creatinine ratio
Change in albuminuria defined as urinary albumin/creatinine ratio: UACR) with dapagliflozin 10mg/d for 24 weeks relative to placebo

Secondary Outcome Measures

systolic and diastolic blood pressure
Change in systolic and diastolic blood pressure: effect of dapagliflozin 10mg/d compared to placebo on change in systolic and diastolic blood pressure
body weight
change in body weight: effect of dapagliflozin 10mg/d compared to placebo on change in body
HbA1c
change in HbA1c: effect of dapagliflozin 10mg/day compared to placebo on change in HbA1c
eGFR
change in eGFR: effect of dapagliflozin 10mg/day compared to placebo on change in eGFR
change in UACR
difference in proportion of patients with ≥30%, 40%, 50% change in UACR from baseline at week 24.: effect of dapagliflozin 10mg/day compared to placebo on the proportion of patients with ≥30%, 40%, 50% change in UACR
number of SAE's and AE's
Safety of dapagliflozin vs Placebo: number of SAE's and AE's reported by the subject or investigator if qualified as: reason for discontinuation, volume depletion, fracture, diabetic ketoacidosis, amputation and adverse events leading to amputation, urinary tract infection, genital infections and hypoglycemia

Full Information

First Posted
December 2, 2021
Last Updated
March 27, 2023
Sponsor
Hiddo Lambers Heerspink
Collaborators
AstraZeneca
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1. Study Identification

Unique Protocol Identification Number
NCT05268926
Brief Title
TreatIng Microalbuminuria Over 24 Weeks in Subjects With or Without Type 2 Diabetes or HYpertension
Acronym
TIMOTHY
Official Title
TreatIng Microalbuminuria Over 24 Weeks in Subjects With or Without Type 2 Diabetes or HYpertension
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
Due to a delayed start-up and delayed patient inclusion in combination with new available scientific data, continuation of the clinical study no longer serves a scientific purpose.
Study Start Date
February 3, 2022 (Actual)
Primary Completion Date
February 2, 2023 (Actual)
Study Completion Date
February 2, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Hiddo Lambers Heerspink
Collaborators
AstraZeneca

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
Yes

5. Study Description

Brief Summary
Rationale: Increased albuminuria has a relatively high prevalence in the general population (5-9%) People with increased albuminuria are more likely to develop progressive kidney and cardiovascular disease compared to persons with no albuminuria. ACE-inhibitors or Angiotensin Receptor Blockers are recommended by clinical practice guidelines to lower albuminuria in patients with hypertension and diabetes. However, despite these drugs decrease albuminuria by approximately 30%, elevated albuminuria remains present in the substantial proportion of persons in the general population. SGLT2 inhibitors are a relatively new class of drugs. Originally they were developed as oral antihyperglycemic drugs. SGLT2 inhibitors have been demonstrated to lower albuminuria and protect the kidney in patients with established chronic kidney disease (CKD) with or without diabetes. Whether the efficacy of SGTL2 inhibitors to lower albuminuria (and possibly confer kidney protection) to persons in the general population (with or without diabetes or hypertension) with persistent albuminuria who generally are at early stages of CKD is unknown. Objective: To assess the albuminuria lowering effects of dapagliflozin in subjects with and without diabetes or hypertension and persistent elevated albuminuria. Study design: Randomized placebo-controlled double blind clinical trial of 24 weeks in duration followed by a 4 weeks wash-out period

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Albuminuria

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Title
Dapagliflozin 10mg/day
Arm Type
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Dapagliflozin 10Mg Tab
Intervention Description
dapagliflozin 10 mg/d or matched placebo
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
urinary albumin/creatinine ratio
Description
Change in albuminuria defined as urinary albumin/creatinine ratio: UACR) with dapagliflozin 10mg/d for 24 weeks relative to placebo
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
systolic and diastolic blood pressure
Description
Change in systolic and diastolic blood pressure: effect of dapagliflozin 10mg/d compared to placebo on change in systolic and diastolic blood pressure
Time Frame
24 weeks
Title
body weight
Description
change in body weight: effect of dapagliflozin 10mg/d compared to placebo on change in body
Time Frame
24 weeks
Title
HbA1c
Description
change in HbA1c: effect of dapagliflozin 10mg/day compared to placebo on change in HbA1c
Time Frame
24 weeks
Title
eGFR
Description
change in eGFR: effect of dapagliflozin 10mg/day compared to placebo on change in eGFR
Time Frame
24 weeks
Title
change in UACR
Description
difference in proportion of patients with ≥30%, 40%, 50% change in UACR from baseline at week 24.: effect of dapagliflozin 10mg/day compared to placebo on the proportion of patients with ≥30%, 40%, 50% change in UACR
Time Frame
24 weeks
Title
number of SAE's and AE's
Description
Safety of dapagliflozin vs Placebo: number of SAE's and AE's reported by the subject or investigator if qualified as: reason for discontinuation, volume depletion, fracture, diabetic ketoacidosis, amputation and adverse events leading to amputation, urinary tract infection, genital infections and hypoglycemia
Time Frame
24 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 45 to 80 years Persistent urinary albumin:creatinine ratio (UACR) ≥ 2.5 mg/mmol (~25 mg/g) Willing to sign informed consent Exclusion Criteria: Diagnosis of type 1 diabetes mellitus eGFR < 25 ml/min/1.73m2 UACR > 3500 mg/g Concurrent treatment with SGLT2 inhibitor Receiving immunosuppressive therapy within 6 months prior to enrolment History of diabetic ketoacidosis Active malignancy aside from treated squamous cell or basal cell carcinoma of the skin. Initiation or changes in the dose of interventions in the renin-angiotensinaldosterone- system, diuretics, GLP-1 receptor agonists within 6 weeks of screening will not be allowed. Any medication, surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of medications including, but not limited to any of the following: History of active inflammatory bowel disease within the last six months; Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last six months; Pancreatic injury or pancreatitis within the last six months; Evidence of hepatic disease as determined by any one of the following: ALT or AST values exceeding 3x ULN at the screening visit, a history of hepatic encephalopathy, a history of esophageal varices, or a history of portocaval shunt; Evidence of urinary obstruction or difficulty in voiding at screening History of severe hypersensitivity or contraindications to dapagliflozin Subjects who, in the assessment of the investigator, may be at risk for dehydration or volume depletion that may affect the interpretation of efficacy or safety data Participation in any clinical intervention study within 3 months prior to initial dosing. History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during the screening. History of noncompliance to medical regimens or unwillingness to comply with the study protocol. Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study. Pregnancy or breastfeeding
Facility Information:
Facility Name
UMCG
City
Groningen
Country
Netherlands

12. IPD Sharing Statement

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TreatIng Microalbuminuria Over 24 Weeks in Subjects With or Without Type 2 Diabetes or HYpertension

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