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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
| University of Colorado, Denver | OTHER |
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SGLT2 inhibitors such as ertugliflozin improve blood pressure and kidney outcomes in people living with diabetes through incompletely understood mechanisms, however, not all patients treated with SGLT2 inhibition have improved outcomes. Changes in kidney sodium handling is among the mechanisms by which SGLT2 inhibition may reduce blood pressure and drive beneficial kidney outcomes. This process is heavily dependent on daily sodium intake by patients receiving SGLT2 inhibitor treatment. In this study, the effect of daily sodium intake on SGLT2-inhibitor induced physiological effect is studied, including blood pressure regulation and kidney physiology.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| moderate-sodium diet; placebo | Placebo Comparator |
| |
| moderate-sodium diet; ertugliflozin 15 once daily | Active Comparator |
| |
| high-sodium diet; placebo | Placebo Comparator |
| |
| High-sodium diet; ertugliflozin 15 mg once daily | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Salt-Diet and/or Ertugliflozin | Other | The interventions consist of an determined amount of dietary sodium intake in combination with either Ertugliflozin 15mg once daily or placebo |
| Measure | Description | Time Frame |
|---|---|---|
| To Investigate the Modifying Effect of Sodium Intake on Ertugliflozin on Blood Pressure | To investigate the modifying effects of WHO-recommended sodium intake (90 mmol per day) vs. high sodium intake (targeted at 250 mmol per day) on the effect of ertugliflozin 15 mg daily, versus placebo, on 24-hour blood pressure in overweight/obese adults with type 2 diabetes | 24 weeks |
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Inclusion Criteria:
Exclusion Criteria:
History of unstable or rapidly progressing renal disease
Estimated GFR <60 mL/min/1.73m2 or eGFR > 90 mL/min/1.73m2 determined by CKD-EPI
UACR > 30 mg/mmol
Current/chronic use of the following medication: SGLT2 inhibitors, TZD, GLP-1RA, glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). Subjects on diuretics will only be excluded when these drugs cannot be stopped for the duration of the study.
Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications (i.e. sports injury, headache or back ache). However, no such drug can be taken within a timeframe of 2 weeks prior to renal testing
History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g. emergency room visit and/or hospitalization) within 1 month prior to the Screening visit.
Current urinary tract infection and active nephritis
Recent (<6 months) history of cardiovascular disease, including:
Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN
History of or actual malignancy (except basal cell carcinoma)
History of or actual severe mental disease
Substance abuse (alcohol: defined as >4 units/day)
Allergy to any of the agents used in the study
Individuals who are investigator site personnel, directly affiliated with the study, or are immediate (spouse, parent, child, or sibling, whether biological or legally adopted) family of investigator site personnel directly affiliated with the study
Inability to understand the study protocol or give informed consent
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amsterdam UMC | Amsterdam | Netherlands |
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Of 61 individuals screened, 41 were enrolled. The required sample size was 34 participants; additional participants were enrolled to account for anticipated dropouts.
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| ID | Title | Description |
|---|---|---|
| FG000 | A - B - C - D | A = moderate sodium diet (90 mmol/day for 20 days) + placebo for 10 days B = moderate sodium diet (90 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days C = high sodium diet ( 250 mmol/day for 20 days) + placebo for 10 days D = high sodium diet ( 250 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days between period washout = 4 weeks |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 22, 2024 |
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While the treatment by ertugliflozin or placebo will be blinded, the sodium interventions are open-label.
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| Ertugliflozin 15 mg | Drug | SGLT2i |
|
| FG001 | A - C - D - B | A = moderate sodium diet (90 mmol/day for 20 days) + placebo for 10 days B = moderate sodium diet (90 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days C = high sodium diet ( 250 mmol/day for 20 days) + placebo for 10 days D = high sodium diet ( 250 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days between period washout = 4 weeks |
| FG002 | B - A - D - C | A = moderate sodium diet (90 mmol/day for 20 days) + placebo for 10 days B = moderate sodium diet (90 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days C = high sodium diet ( 250 mmol/day for 20 days) + placebo for 10 days D = high sodium diet ( 250 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days between period washout = 4 weeks |
| FG003 | B - D - C - A | A = moderate sodium diet (90 mmol/day for 20 days) + placebo for 10 days B = moderate sodium diet (90 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days C = high sodium diet ( 250 mmol/day for 20 days) + placebo for 10 days D = high sodium diet ( 250 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days between period washout = 4 weeks |
| FG004 | C - A - B - D | A = moderate sodium diet (90 mmol/day for 20 days) + placebo for 10 days B = moderate sodium diet (90 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days C = high sodium diet ( 250 mmol/day for 20 days) + placebo for 10 days D = high sodium diet ( 250 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days between period washout = 4 weeks |
| FG005 | C - B - D - A | A = moderate sodium diet (90 mmol/day for 20 days) + placebo for 10 days B = moderate sodium diet (90 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days C = high sodium diet ( 250 mmol/day for 20 days) + placebo for 10 days D = high sodium diet ( 250 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days between period washout = 4 weeks |
| FG006 | D - A - B - C | A = moderate sodium diet (90 mmol/day for 20 days) + placebo for 10 days B = moderate sodium diet (90 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days C = high sodium diet ( 250 mmol/day for 20 days) + placebo for 10 days D = high sodium diet ( 250 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days between period washout = 4 weeks |
| FG007 | D - A - C - B | A = moderate sodium diet (90 mmol/day for 20 days) + placebo for 10 days B = moderate sodium diet (90 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days C = high sodium diet ( 250 mmol/day for 20 days) + placebo for 10 days D = high sodium diet ( 250 mmol/day for 20 days) + ertugliflozin 15mg per day for 10 days between period washout = 4 weeks |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Baseline Characteristics | In total, 34 participants were included |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean age of population with standard deviation | Mean | Standard Deviation | years |
| ||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| BMI | Median | Inter-Quartile Range | kg/m² |
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| Hba1c | Median | Inter-Quartile Range | % glycated hemoglobin |
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| eGFR | Mean | Standard Deviation | mL/min/1.73 m² |
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| systolic blood pressure | Mean | Standard Deviation | mmHg |
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| diastolic blood pressure | Mean | Standard Deviation | mmHg |
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| Urinary volume | Median | Inter-Quartile Range | mL |
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| 24 hour urinary sodium excretion | Median | Inter-Quartile Range | mmol |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | To Investigate the Modifying Effect of Sodium Intake on Ertugliflozin on Blood Pressure | To investigate the modifying effects of WHO-recommended sodium intake (90 mmol per day) vs. high sodium intake (targeted at 250 mmol per day) on the effect of ertugliflozin 15 mg daily, versus placebo, on 24-hour blood pressure in overweight/obese adults with type 2 diabetes | Posted | Mean | Standard Deviation | mmHg | 24 weeks |
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From screening until the last day of the 4th intervention period, up to approximately 24 weeks. Each intervention period lasted 20 days, with 4-week washout periods between intervention periods.
All cause mortality risk = 0, and there were no serious adverse events. There were some (not serious) adverse events that occurred on the individual level, so in <5%, therefore, these were not reported.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Moderate-sodium Diet; Placebo | Participants adhered to moderate sodium intake for 20 days (aimed at 90 mmols sodium per day) verified by 24 hour urine collection after 10 days. Then participants received placebo for 10 days. | 0 | 34 | 0 | 34 | 0 | 34 |
| EG001 | Moderate-sodium Diet; Ertugliflozin 15 Once Daily | Participants adhered to moderate sodium intake for 20 days (aimed at 90 mmols sodium per day) verified by 24 hour urine collection after 10 days. Then participants received ertugliflozin for 10 days. | 0 | 34 | 0 | 34 | 2 | 34 |
| EG002 | High-sodium Diet; Placebo | Participants adhered to high sodium intake for 20 days (aimed at 250 mmols sodium per day) verified by 24 hour urine collection after 10 days. Then participants received placebo for 10 days. | 0 | 34 | 0 | 34 | 0 | 34 |
| EG003 | High-sodium Diet; Ertugliflozin 15 mg Once Daily | Participants adhered to high sodium intake for 20 days (aimed at 250 mmols sodium per day) verified by 24 hour urine collection after 10 days. Then participants received ertugliflozin for 10 days. | 0 | 34 | 0 | 34 | 0 | 34 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| genital infection | Infections and infestations | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Daniël van Raalte | Amsterdam UMC | +31-20-4440534 | d.vanraalte@amsterdamumc.nl |
| Jan 26, 2026 |
| Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D003928 | Diabetic Nephropathies |
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D048909 | Diabetes Complications |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C570288 | ertugliflozin |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| diastolic blood pressure |
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| Mixed Models Analysis |
| 0.0657 |
| Mean Difference (Final Values) |
| -2.1 |
| Standard Error of the Mean |
| 1.1 |
| Superiority |
| systolic blood pressure lowering effect of ertugliflozin versus placebo during high sodium intake. | Mixed Models Analysis | 0.0042 | Mean Difference (Final Values) | -5.2 | Standard Error of the Mean | 1.8 | Superiority |
| diastolic blood pressure lowering effect of ertugliflozin versus placebo during high sodium intake. | Mixed Models Analysis | 0.0394 | Mean Difference (Final Values) | -2.4 | Standard Error of the Mean | 1.1 | Superiority |