## Protocol Section
### Identification Module
**NCT ID:** NCT06421870

**Brief Title:** Renoprotective Effects of Dapagliflozin Versus Pentoxiphylline in Chronic Kidney Disease Patients

**Official Title:** Renoprotective Effects of Dapagliflozin Versus Pentoxiphylline in Chronic Kidney Disease Patients

#### Organization Study ID Info
**ID:** MD277/2023
#### Organization
**Class:** OTHER
**Full Name:** Ain Shams University
### Status Module
#### Completion Date
**Date:** 2025-07

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-20

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-15

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2025-05

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-03-01

**Type:** ACTUAL

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-20
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-15
**Study First Submit QC Date:** 2024-05-15
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Ain Shams University

#### Responsible Party

**Investigator Affiliation:** Ain Shams University

**Investigator Full Name:** nahla mohamed elsayed teama

**Investigator Title:** Assistant Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Is US Export:** False

### Description Module

**Brief Summary:** Kidneys have a vital role in glucose homeostasis by various mechanisms, one of the major mechanisms is through SGLT2. This role was commonly overlooked till development of the new SGLT2 inhibitors. (Ni, L., et al 2020) The SGLT2 inhibitor class of glucose-lowering agents has recently shown beneficial effects to reduce the onset and progression of renal complications in people with and without diabetes, through slow the decline in glomerular filtration rate (GFR), delaying the onset of microalbuminuria and slow or reverse the progression of proteinuria. (Nespoux, J., \& Vallon, V. 2020) The drug pentoxifylline is a methyl-xanthine derivative and a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative and antifibrotic actions currently indicated for peripheral artery disease. (Panchapakesan U et al.,2018) Chronic kidney disease is a progressive disorder in which patients are treated according to complications presented such as hypocalcemia, hyperkalemia, anemia and metabolic acidosis.

**Detailed Description:** It is only in recent years that the attention was drawn on the key role of the kidney in glucose homeostasis. Nevertheless, along with the liver, the kidney has a key role in ensuring the energy needs during fasting periods. This organ has a vital role in absorbing the entire quantity of the filtered glucose. Having a glomerular filtration rate of 180 litres per day, it filters approximately 180 grams of glucose per day, bringing its contribution in maintaining normal fasting plasma glucose (FPG) levels. (Cersosimo, E.et al 2014) The reabsorption of glucose is ensured by the sodium-glucose cotransporter (SGLT) 2, responsible for the reabsorption of 90% of glucose, and SGLT1, that reabsorbs the remaining glucose. (Mota, M., et al 2015) Glomerular hyperfiltration is a common pathway of kidney injury both in diabetic and non-diabetic settings and is associated with progression of kidney function decline. (Hoogeveen, E. K. 2022) Sodium-glucose co-transporter-2 (SGLT2) inhibitors are glucose-lowering agents that eliminate excess glucose through a glucosuric effect by reducing glucose reabsorption from the renal filtrate (Thomson, S. C., et al. 2019) It is indicated that the expression of high mobility group box 1 (HMGB1) increased in patients with kidney disease, and may result in renal injury through the activation of nuclear factor- κB (NF- κB) and an increase in receptor for advanced glycation end products (RAGE) expression. It is suggested that Dapagliflozin achieves its reno-protective status through its antioxidative stress and anti-inflammatory action via inhibition of the HMGB1 - RAGE - NF- κB signalling pathway. (Yao, D et al., 2018) SGLT2 is found almost exclusively in the luminal membranes of epithelial cells lining the first and second segments of the proximal tubules, where it mediates reabsorption of most (typically ≥ 90%) of filtered glucose. (Mudaliar S, et al. 2015) By inhibiting SGLT2 beneficial kidney effects are thought to be mediated by various mechanisms, including restoration of tubule-glomerular feedback leading to a reduction in intraglomerular pressure and hyperfiltration. Both conditions are considered core components of the pathophysiology contributing to progression of diabetic as well as nondiabetic CKD. Reductions in intraglomerular pressure, as shown by agents blocking the renin-angiotensin system, are frequently accompanied by a hemodynamic acute decrease in GFR, which is reversible after treatment cessation. (Wanner et al., 2018).

Common drug side effects of dapagliflozin include urinary tract infections, cystitis, hypotension, dehydration and female genital mycotic infections. Hypoglycemic episodes were reported in 6% to 10% of patients who administer dapagliflozin concurrently with insulin and insulin secretagogues. (Anderson SL et al., 2014) Pentoxifylline (PTF) is a synthetic dimethylxanthine derivative that modulates the rheological properties of blood and has both anti-oxidant and anti-inflammatory properties. PTF has been investigated for its possible use in diverse conditions, including osteoradionecrosis, diabetic kidney disease, and generally any condition associated with fibrosis. (Wen WX et al., 2017) PTF reduces levels of inflammatory markers: high-sensitivity C-reactive protein (hs-CRP), serum fibrinogen and TNF-α, this could reduce albuminuria and slow renal disease progression. (de Morales AM et al, 2019)

Thus, we need to evaluate the effect of Dapagliflozin versus Pentoxifylline on GFR among CKD non-diabetic patients.

### Conditions Module

**Conditions:**

- Chronic Kidney Diseases

**Keywords:**

- Dapagliflozin

- Chronic kidney disease

- Pentoxiphylline

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 210

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 70 patients will take dapagliflozin 10 mg per day for 1 year in addition to standard management for chronic kidney disease

**Intervention Names:**

- Drug: Dapagliflozin 10mg Tab

**Label:** Dapagliflozin arm

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** 70 patients will take pentoxifylline 400 mg twice daily for 1 year in addition to standard management for chronic kidney disease

**Intervention Names:**

- Drug: Pentoxifylline 400 MG

**Label:** Pentoxiphylline arm

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Description:** 70 patients won't take either dapagliflozin or pentoxiphylline but they will continue their standard management for chronic kidney disease

**Label:** Control

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Dapagliflozin arm

**Description:** Patients will be given dapagliflozin 10 mg once daily

**Name:** Dapagliflozin 10mg Tab

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Pentoxiphylline arm

**Description:** Patients will be given pentoxyifylline 400 mg twice daily

**Name:** Pentoxifylline 400 MG

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** eGFR will be based on serum creatinine and will be calculated by CKD-EPI 2021

**Measure:** Change in estimated glomerular filtration rate

**Time Frame:** 1 year

**Description:** Proteinuria quantification done by urine protein to creatinine ratio

**Measure:** Change in proteinuria

**Time Frame:** 1 year

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* CKD stage 2 and 3

Exclusion Criteria:

* Diabetes mellitus
* History of recurrent or recent genitourinary infections
* Immunosuppressive medications
* Malignancy

**Maximum Age:** 60 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** Mohammed.Ashraf@med.asu.edu.eg

**Name:** Mohamed A Mohamed, MSc

**Phone:** 1119090018

**Phone Ext:** +20

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Cairo

**Contacts:**

***Contact 1:***

- **Email:** Mohammed.Ashraf@med.asu.edu.eg

- **Name:** Mohamed A Mohamed, MSc

- **Phone:** 1119090018

- **Phone Ext:** +20

- **Role:** CONTACT

**Country:** Egypt

**Facility:** Ain Shams University

**Status:** RECRUITING

**Zip:** 1181

#### Overall Officials

**Official 1:**

**Affiliation:** Ain Shams University

**Name:** Saeed A Saeed, Professor

**Role:** STUDY_DIRECTOR

### References Module

#### References

**Citation:** Ni L, Yuan C, Chen G, Zhang C, Wu X. SGLT2i: beyond the glucose-lowering effect. Cardiovasc Diabetol. 2020 Jun 26;19(1):98. doi: 10.1186/s12933-020-01071-y.

**PMID:** 32590982

**Citation:** Nespoux J, Vallon V. Renal effects of SGLT2 inhibitors: an update. Curr Opin Nephrol Hypertens. 2020 Mar;29(2):190-198. doi: 10.1097/MNH.0000000000000584.

**PMID:** 31815757

**Citation:** Panchapakesan U, Pollock C. Drug repurposing in kidney disease. Kidney Int. 2018 Jul;94(1):40-48. doi: 10.1016/j.kint.2017.12.026. Epub 2018 Apr 6.

**PMID:** 29628139

**Citation:** Cersosimo E, Solis-Herrera C, Triplitt C. Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients. J Bras Nefrol. 2014 Jan-Mar;36(1):80-92. doi: 10.5935/0101-2800.20140014.

**PMID:** 24676619

**Citation:** DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab. 2012 Jan;14(1):5-14. doi: 10.1111/j.1463-1326.2011.01511.x.

**PMID:** 21955459

## 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: D000051437

- Term: Renal Insufficiency

- ID: D000002908

- Term: Chronic Disease

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BXS

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

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10698

- Name: Kidney Diseases

- Relevance: HIGH

- As Found: Kidney Disease

- ID: M26717

- Name: Renal Insufficiency, Chronic

- Relevance: HIGH

- As Found: Chronic Kidney Disease

- ID: M26718

- Name: Renal Insufficiency

- Relevance: LOW

- As Found: Unknown

- 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: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: HIGH

- As Found: Chronic

### Condition Browse Module - Meshes

- ID: D000007674

- Term: Kidney Diseases

- ID: D000051436

- Term: Renal Insufficiency, Chronic

### 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

- ID: D000010726

- Term: Phosphodiesterase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000010975

- Term: Platelet Aggregation Inhibitors

- ID: D000011837

- Term: Radiation-Protective Agents

- ID: D000020011

- Term: Protective Agents

- ID: D000014665

- Term: Vasodilator Agents

- ID: D000016166

- Term: Free Radical Scavengers

- ID: D000000975

- Term: Antioxidants

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: VaDiAg

- Name: Vasodilator Agents

- Abbrev: PlAggInh

- Name: Platelet Aggregation Inhibitors

### Intervention Browse Module - Browse Leaves

- ID: M348449

- Name: Dapagliflozin

- Relevance: HIGH

- As Found: COPD

- ID: M13342

- Name: Pentoxifylline

- Relevance: HIGH

- As Found: Manufacturer

- ID: M1691

- Name: Sodium-Glucose Transporter 2 Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M13629

- Name: Phosphodiesterase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M13865

- Name: Platelet Aggregation Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M21869

- Name: Protective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M14684

- Name: Radiation-Protective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M17412

- Name: Vasodilator Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4292

- Name: Antioxidants

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000529054

- Term: Dapagliflozin

- ID: D000010431

- Term: Pentoxifylline

### Misc Info Module

- Version Holder: 2024-05-31
