## Protocol Section
### Identification Module
**NCT ID:** NCT06435858

**Acronym:** SIDIA

**Brief Title:** Short-term Effects of an SGLT2 Inhibitor on Divalent Ions in Autosomal Dominant Polycystic Kidney Disease

**Official Title:** Short-term Effects of an SGLT2 Inhibitor on Divalent Ions in Autosomal Dominant Polycystic Kidney Disease

#### Organization Study ID Info
**ID:** 2024-00070
#### Organization
**Class:** OTHER
**Full Name:** Cantonal Hospital Graubuenden
### Status Module
#### Completion Date
**Date:** 2024-12

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-30

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-24

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2024-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09-01

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-30
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-24
**Study First Submit QC Date:** 2024-05-24
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** University of Zurich

#### Lead Sponsor

**Class:** OTHER

**Name:** Cantonal Hospital Graubuenden

#### Responsible Party

**Investigator Affiliation:** Cantonal Hospital Graubuenden

**Investigator Full Name:** Patrick Hofmann

**Investigator Title:** MD

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This study aims to better understand electrolyte handling in patients with autosomal dominant polycystic kidney disease treated with the SGLT2 inhibitor Empagliflozin.

Patients will be randomized into two groups and take Empagliflozin or a Placebo for 2 weeks with a wash-out period of 2 weeks. The primary outcome is tubular handling of the divalent ions calcium, phosphate and magnesium. Secondary outcomes include diuresis, safety and tolerability.

**Detailed Description:** This investigator-initiated randomised, single-blind, placebo-controlled cross-over study aims to better understand tubular electrolyte handling of divalent ions in patients with autosomal dominant polycystic kidney disease treated with the SGLT2 inhibitor Empagliflozin.

After randomization, at week 0, participants collect 24-hour urine sample and a patient visit to assess vitals and blood tests takes place. After this visit, period 1 starts with a 2-week treatment of either Empagliflozin 10mg or Placebo.

At week 2, the second 24-hour-urine sample and 2. patient visit and blood test take place. After this visit, wash-out period for 2 weeks starts where no study drug will be administered At week 4, the period 2, the crossover-period starts for an additional 2 weeks. At week 6; a final and third 24-hour urine sample, clinical visit and blood test takes place.

At week 3 \&amp; 7, a phone consultation will assess safety.

### Conditions Module

**Conditions:**

- Autosomal Dominant Polycystic Kidney Disease

**Keywords:**

- phosphate

- calcium

- magnesium

- Empagliflozin

- ADPKD

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** Investigator-initiated randomised, single-blind, placebo-controlled, cross-over study

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- PARTICIPANT

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 40

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Empagliflozin 10mg

**Intervention Names:**

- Drug: Empagliflozin

**Label:** Intervention

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Placebo

**Intervention Names:**

- Drug: Placebo

**Label:** Control

**Type:** PLACEBO_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Intervention

**Description:** Empagliflozin 10mg

**Name:** Empagliflozin

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Control

**Description:** Placebo capsule

**Name:** Placebo

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** - Ca2+, phosphate, Mg absolutely and measured by fractional excretions

**Measure:** Primary Outcome

**Time Frame:** After a two week intervention

#### Secondary Outcomes

**Description:** - diuresis (24-hour urine volume, 24-hour creatinine, ketonuria, osmolarity, urinary pH) - tubular handling of other electrolytes (Na, K, Cl) - inflammation metabolism (CRP, hemoglobin?) - kidney function (creatinine, uric acid, urea, hemoglobin?) - effect on standardized blood pressure (assessed every two weeks) - bone metabolism (FGF23, PTH, 25-(OH)-D3) - tolerability (patient-reported side effects (nycturia, urinary urgency, lightheadedness, syncope) - safety (bacteriuria, urinary tract infection requiring antibiotic treatment, genital mycosis)

**Measure:** Secondary Outcome

**Time Frame:** After a two week intervention

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* - Patients 18-75 years old with ADPKD, defined according to international diagnostic and classification criteria14, treated at Cantonal Hospital Graubünden (KSGR) and the University Hospital Zürich (USZ) independent of baseline treatment with the vasopressin receptor antagonist Tolvaptan
* Informed consent as documented by signature

Exclusion Criteria:

* - renal replacement therapy or kidney allograft recipient
* chronic kidney disease CKD KDIGO Stage G4 (eGFR under 30ml/min/1.73m2)
* patients younger 18 years of age
* Diabetes mellitus type 1
* recurrent urinary tract infections (UTI) defined as more than 3 infections requiring antibiotic treatment or over 1 requiring hospitalization/year.
* Patients with uncontrolled hypertension (defined as ambulatory systolic BP over 180mmHg), liver cirrhosis (Child Pugh B and C)
* Patients not able or not willing to stop the following medications during the study period of participation in the trial:
* Thiazide diuretics
* Carbonic anhydrase inhibitors
* Sodium bicarbonate
* 1, 25 (OH) vitamin D (calcitriol)
* Bisphosphonate, denosumab, teriparatide
* Pregnant or lactating women
* Known allergy to study drug
* Inability to understand and follow the protocol

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** hofmannpatrick@bluewin.ch

**Name:** Patrick Hofmann, MD

**Phone:** +4181 256 6305

**Role:** CONTACT

**Contact 2:**

**Email:** medizin@ksgr.ch

**Name:** Thomas Fehr, MD

**Phone:** +4181 256 6305

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Chur

**Contacts:**

***Contact 1:***

- **Email:** medizin@ksgr.ch

- **Name:** Patrick Hofmann, MD

- **Role:** CONTACT

***Contact 2:***

- **Name:** Lorena Roth, MD

- **Role:** SUB_INVESTIGATOR

**Country:** Switzerland

**Facility:** Cantonal Hospital Graubuenden

**State:** Graubuenden

**Zip:** 7000

#### Overall Officials

**Official 1:**

**Affiliation:** Cantonal Hospital Graubuenden

**Name:** Thomas Fehr, MD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Cantonal Hospital Graubuenden

**Name:** Patrick Hofmann, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** The local ethics committee approval does not include individual participant data sharing.

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000014570

- Term: Urologic Diseases

- ID: D000052776

- Term: Female Urogenital Diseases

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000052801

- Term: Male Urogenital Diseases

- ID: D000007592

- Term: Joint Diseases

- ID: D000009140

- Term: Musculoskeletal Diseases

- ID: D000009135

- Term: Muscular Diseases

- ID: D000009139

- Term: Musculoskeletal Abnormalities

- ID: D000000013

- Term: Congenital Abnormalities

- ID: D000052177

- Term: Kidney Diseases, Cystic

- ID: D000000015

- Term: Abnormalities, Multiple

- ID: D000072661

- Term: Ciliopathies

- ID: D000030342

- Term: Genetic Diseases, Inborn

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC16

- Name: Diseases and Abnormalities at or Before Birth

- Abbrev: BC05

- Name: Musculoskeletal Diseases

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10698

- Name: Kidney Diseases

- Relevance: HIGH

- As Found: Kidney Disease

- ID: M10712

- Name: Polycystic Kidney Diseases

- Relevance: HIGH

- As Found: Polycystic Kidney Disease

- ID: M19237

- Name: Polycystic Kidney, Autosomal Dominant

- Relevance: HIGH

- As Found: Autosomal Dominant Polycystic Kidney

- ID: M4484

- Name: Arthrogryposis

- Relevance: HIGH

- As Found: Autosomal Dominant

- ID: M17319

- Name: Urologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M27095

- Name: Male Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10621

- Name: Joint Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12097

- Name: Musculoskeletal Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12092

- Name: Muscular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12

- Name: Congenital Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M12096

- Name: Musculoskeletal Abnormalities

- Relevance: LOW

- As Found: Unknown

- ID: M26983

- Name: Kidney Diseases, Cystic

- Relevance: LOW

- As Found: Unknown

- ID: M14

- Name: Abnormalities, Multiple

- Relevance: LOW

- As Found: Unknown

- ID: M1076

- Name: Ciliopathies

- Relevance: LOW

- As Found: Unknown

- ID: M23686

- Name: Genetic Diseases, Inborn

- Relevance: LOW

- As Found: Unknown

- ID: T591

- Name: Autosomal Dominant Multiple Pterygium Syndrome

- Relevance: HIGH

- As Found: Autosomal Dominant

- ID: T493

- Name: Arthrogryposis Multiplex Congenita

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001176

- Term: Arthrogryposis

- ID: D000007674

- Term: Kidney Diseases

- ID: D000007690

- Term: Polycystic Kidney Diseases

- ID: D000016891

- Term: Polycystic Kidney, Autosomal Dominant

### Intervention Browse Module - Ancestors

- ID: D000077203

- Term: Sodium-Glucose Transporter 2 Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: BDCA

- Name: Bone Density Conservation Agents

### Intervention Browse Module - Browse Leaves

- ID: M258082

- Name: Empagliflozin

- Relevance: HIGH

- As Found: Part 1

- ID: M5381

- Name: Calcium

- Relevance: LOW

- As Found: Unknown

- ID: M5398

- Name: Calcium, Dietary

- Relevance: LOW

- As Found: Unknown

- ID: M1691

- Name: Sodium-Glucose Transporter 2 Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000570240

- Term: Empagliflozin

### Misc Info Module

- Version Holder: 2024-05-31
