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

Type 2 Diabetes Mellitus Clinical Trial

— PENFOSIDINE  

Official title:

Pentoxifylline Effect on Renal Function, Oxidative Stress, Inflammation, and Fibrosis Markers, and Quality of Life in Patients With Diabetic Nephropathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03664414
• Other study ID #: CNIC-2015-785-065
• Status: Recruiting
• Phase: Phase 4
• Start date: March 1, 2018
• Est. completion date: December 31, 2021

Study information

• Verified date: February 2019
• Source: Coordinación de Investigación en Salud, Mexico
• Contact: Maria Eugenia Galván Plata, M. D
• Phone: +015556276900
• Email: eugenia.galvan[@]imss.gob.mx
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 196
• Est. completion date: December 31, 2021
• Est. primary completion date: July 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Disease stage3 and 4
• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Diabetic Nephropathies
• Kidney Diseases
• Renal Insufficiency, Chronic
• Type 2 Diabetes Mellitus

Intervention

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

Locations

Country	Name	City	State
Mexico	Cibimi - Hgz 83 Imss	Morelia	Michoacán

Sponsors (5)

Lead Sponsor	Collaborator
Maria Eugenia Galván Plata	Centro de Investigación Biomédica de Michoacán., Coordinación Auxiliar Medica de Investigación en Salud. Delegación Michoacán., Hospital General de Zona N° 83 Instituto Mexicano del Seguro Social., Hospital General Regional N° 1 Instituto Mexicano del Seguro Social.

Country where clinical trial is conducted

Mexico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the glomerular filtration rate	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)	The measurements will be done baseline and every six months up to 24 months.
Secondary	Change in oxidative stress marker.	The change in vit C level from baseline (normal range 4-8.8mg/ L)	Change is assessed baseline, 6 months, 12 months, 18 months and 24 months.
Secondary	Change in fibrosis markers.	Change in Nt_ProBNP from the baseline (Normal values up to 381 pg/mL)	Change is assessed baseline, 6 months, 12 months, 18 months and 24 months.
Secondary	Change in inflammation markers.	To assess inflammation high sensitivity C reactive protein will be measured by nephelometry. (normal value < 5 mg/L	Change is assessed baseline, 6 months, 12 months, 18 months and 24 months.
Secondary	Change in health-related quality of life	This outcome will be measured by the SF 36 questionnaire, themaximun punctuation is 100, as greater punctuation a better quality of life	The questionnaire will be applied baseline and every six months up to 24 months.