Pentoxifylline Effect in Patients With Diabetic Nephropathy.(PENFOSIDINE STUDY) (PENFOSIDINE)

• ClinicalTrials.gov Identifier: NCT03664414
• Recruitment Status: Unknown
• First Posted: September 10, 2018
• Last Update Posted: February 7, 2019
• Sponsor: Maria Eugenia Galván Plata
• Collaborators: Centro de Investigación Biomédica de Michoacán.; Hospital General Regional N° 1 Instituto Mexicano del Seguro Social.; Hospital General de Zona N° 83 Instituto Mexicano del Seguro Social.; Coordinación Auxiliar Medica de Investigación en Salud. Delegación Michoacán.
• Information provided by (Responsible Party): Maria Eugenia Galván Plata, Coordinación de Investigación en Salud, Mexico

Study Description

Brief Summary:

One of the purposes of the management of the patient with chronic kidney disease (CKD)is to slow the decline of renal function. The mechanisms by which the renal function declines involve inflammatory and fibrotic responses due in part by the effects of oxidative stress. Pentoxifylline (PTX)is a drug that stimulates adenosine receptors, and produces inhibition of phosphodiesterases, as well as being a dopaminergic modulator through D1 and D2 receptors. Its main effects are inhibition of the inflammatory state by decreasing serum levels of tumor necrosis factor alpha (TNF-ɒ) and monocyte chemo attractant protein 1 (MCP_1), which may slow down the decline of renal function. It also produces diminish of sympathetic activity, with the reduction of circulating levels of norepinephrine (NA), which may contribute to the reduction of glomerulosclerosis in diabetic patients. In the connective tissue increases the activity of the collagenases and decrease of collagen, fibronectin and glucosamine of the fibroblasts as well as inhibition of oxygen free radicals. Due to its antioxidant, anti-inflammatory and anti-fibrotic effects, PTX can result in an excellent therapeutic option for the prevention of CKD in DM2.

This work proposes the use of pentoxifylline as treatment CKD in DM2. Its application in patients with CKD will allow a therapeutic management with different targets, for its antioxidant, anti-inflammatory and antifibrotic effects that will be evaluated by means of fibrosis, inflammation and oxidative stress markers. The results will be of great importance in clinical practice, since they will justify the use of a new pharmacological tool, already known, with minimal adverse effects and low cost, accessible to all strata of the population since it is found as generic.

Condition or disease	Intervention/treatment	Phase
Chronic Kidney Disease stage3 and 4; Type 2 Diabetes Mellitus	Drug: pentoxifylline	Phase 4

Detailed Description:

Patients will be randomly selected from the outpatient family medicine clinics. Once included, patients will be randomly allocated (by a computer-generated randomization list) to a study or control group. Over a period of 2 years, patients of the study group will receive one PTX tablet (400 mg) orally three times a day (at dinner time), whereas controls will receive one cellulose identical tablet on the same schedule.

All patients will continue with their usual treatment prescribed by their family doctor. Monthly visits will be scheduled for clinical and biochemical evaluations. A blood sample will be taken at baseline and every six months up to 24 months, for measurement of complete blood count, urea, creatinine, glucose, albumin, lipids, electrolytes, liver function tests, serum total proteins, (will be measure by usual methods). In serum samples at 0, 6, 12, 18 and 24 months, high sensibility C reactive protein will be measured by nephelometry, Brain natriuretic peptide and Serum Cystatin C will be measured by ELISA. Glomerular filtration rate (GFR) will be calculated based in Cystatin C level Grubb's equations. Vitamin C will be measured by HPLC. A 24 h ambulatory blood pressure monitoring (24 h ABPM), M-mode and two-dimensional echocardiographic, and an analysis of body composition by bioelectrical impedance will be done at baseline 6, 12, 18 and 24 months. To investigate health-related quality of life the short-form 36 (SF-36) questionnaire will be applied. Treatment compliance will be recorded by counting tablets left in the container at the end of each monthly visit and by the Morinsky Green test.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 196 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: blinded,multicenter, randomized, pentoxifylline vs placebo controlled clinical trial. Time: two years after the enrollment of the last patient.
• Masking: Double (Participant, Investigator)
• Masking Description: Plaebo controlled
• Primary Purpose: Treatment
• Official Title: Pentoxifylline Effect on Renal Function, Oxidative Stress, Inflammation, and Fibrosis Markers, and Quality of Life in Patients With Diabetic Nephropathy
• Actual Study Start Date: March 1, 2018
• Estimated Primary Completion Date: July 30, 2019
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo group; Placebo group will receive 1 tablet of cellulose pill to mimic pentoxifylline tablets three times a day with meals, during the following two years.	Drug: pentoxifylline; Pentoxifylline or placebo will be prescribed three times a day with meals. All the participants will continue with the usual treatment. Time frame: two years; Other Name: Trental
Active Comparator: Pentoxifylline group; Pentoxifillyne or experimental group will receive 400 mg of pentoxifylline three times a day with meals, during the following two years.	Drug: pentoxifylline; Pentoxifylline or placebo will be prescribed three times a day with meals. All the participants will continue with the usual treatment. Time frame: two years; Other Name: Trental

Outcome Measures

Primary Outcome Measures :

1. Change in the glomerular filtration rate [ Time Frame: The measurements will be done baseline and every six months up to 24 months. ]
   It will be measure as to duplicate serum creatinine levels from baseline (mg/dL), or to pass from a stage of chronic kidney disease to he next stage (GFR mL/min)

Secondary Outcome Measures :

1. Change in oxidative stress marker. [ Time Frame: Change is assessed baseline, 6 months, 12 months, 18 months and 24 months. ]
   The change in vit C level from baseline (normal range 4-8.8mg/ L)
2. Change in fibrosis markers. [ Time Frame: Change is assessed baseline, 6 months, 12 months, 18 months and 24 months. ]
   Change in Nt_ProBNP from the baseline (Normal values up to 381 pg/mL)
3. Change in inflammation markers. [ Time Frame: Change is assessed baseline, 6 months, 12 months, 18 months and 24 months. ]
   To assess inflammation high sensitivity C reactive protein will be measured by nephelometry. (normal value < 5 mg/L
4. Change in health-related quality of life [ Time Frame: The questionnaire will be applied baseline and every six months up to 24 months. ]
   This outcome will be measured by the SF 36 questionnaire, themaximun punctuation is 100, as greater punctuation a better quality of life

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. CKD
2. Type 2 diabetes mellitus
3. Microalbuminuria
4. Proteinuria.
5. Creatinine plasma clearance ˂ of 60 mL / min.

Exclusion criteria:

1. History of psychiatric disorders,
2. Immunosuppressants treatment
3. Herbalism Treatment
4. History of chronic alcoholism.
5. Type 1 diabetes mellitus.
6. Chronic obstructive pulmonary disease.
7. Pulmonary fibrosis
8. Heart failure
9. HIV-AIDS.
10. Liver cirrhosis.
11. Chronic hepatitis.

Contacts and Locations

Contacts

Contact: Maria Eugenia Galván Plata, M. D; +015556276900 ext 21230; eugenia.galvan@imss.gob.mx

Contact: Carla A Carla Martínez Castuera Gómez, MD; +015556276900 ext 21218; carla.martinez@imss.gob.mx

Locations

Mexico

Cibimi - Hgz 83 Imss; Recruiting

Morelia, Michoacán, Mexico, 58290

Contact: Oliva Mejía - Rodríguez, PhD 01 4431853008 oliva.mejia@imss.gob.mx

Sponsors and Collaborators

Maria Eugenia Galván Plata

Centro de Investigación Biomédica de Michoacán.

Hospital General Regional N° 1 Instituto Mexicano del Seguro Social.

Hospital General de Zona N° 83 Instituto Mexicano del Seguro Social.

Coordinación Auxiliar Medica de Investigación en Salud. Delegación Michoacán.

Investigators

• Principal Investigator: Oliva Mejía-Rodríguez, PhD; CIBIMI IMSS

More Information

• Responsible Party: Maria Eugenia Galván Plata, Coordinacion de Investigacion en Salud, México, Coordinación de Investigación en Salud, Mexico
• ClinicalTrials.gov Identifier: NCT03664414
• Other Study ID Numbers: CNIC-2015-785-065
• First Posted: September 10, 2018
• Last Update Posted: February 7, 2019
• Last Verified: February 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The individual participant data for all primary and secondary outcome measures will be made available
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Data will be available six months after the end of the study
• Access Criteria: Data access request will be reviewed by the research institutional board.

• 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

Keywords provided by Maria Eugenia Galván Plata, Coordinación de Investigación en Salud, Mexico:

oxidative stress; fibrosis; inflammation; quality of life

Additional relevant MeSH terms:

Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies; Diabetes Mellitus, Type 2; Urologic Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Renal Insufficiency; Diabetes Complications; Pentoxifylline; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Radiation-Protective Agents; Protective Agents; Physiological Effects of Drugs; Vasodilator Agents; Free Radical Scavengers; Antioxidants