Clinical trial NCT03664414: Pentoxifylline Effect in Patients With Diabetic Nephropathy.(PENFOSIDINE STUDY)
Official title: Pentoxifylline Effect on Renal Function, Oxidative Stress, Inflammation, and Fibrosis Markers, and Quality of Life in Patients With Diabetic Nephropathy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Kidney Disease stage3 and 4
Type 2 Diabetes Mellitus
Keywords: oxidative stress
fibrosis
inflammation
quality of life
Lead sponsor: Coordinación de Investigación en Salud, Mexico
Sponsor class: OTHER_GOV
Collaborators: name: Centro de Investigación Biomédica de Michoacán.
name: Hospital General Regional N° 1 Instituto Mexicano del Seguro Social.
name: Hospital General de Zona N° 83 Instituto Mexicano del Seguro Social.
name: Coordinación Auxiliar Medica de Investigación en Salud. Delegación Michoacán.
First posted: 2018-09-10
Enrollment: 196
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: blinded,multicenter, randomized, pentoxifylline vs placebo controlled clinical trial. Time: two years after the enrollment of the last patient.
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Change in the glomerular filtration rate
timeFrame: The measurements will be done baseline and every six months up to 24 months.
Secondary outcomes:
measure: Change in oxidative stress marker.
timeFrame: Change is assessed baseline, 6 months, 12 months, 18 months and 24 months.
measure: Change in fibrosis markers.
timeFrame: Change is assessed baseline, 6 months, 12 months, 18 months and 24 months.
measure: Change in inflammation markers.
timeFrame: Change is assessed baseline, 6 months, 12 months, 18 months and 24 months.
measure: Change in health-related quality of life
timeFrame: The questionnaire will be applied baseline and every six months up to 24 months.
Other outcomes:
Locations:
city: Morelia
country: Mexico
facility: Cibimi - Hgz 83 Imss
state: Michoacán
Study officials:
affiliation: CIBIMI IMSS
name: Oliva Mejía-Rodríguez, PhD
role: PRINCIPAL_INVESTIGATOR
References: