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

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ClinicalTrials.gov Identifier: NCT03664414
Recruitment Status : Recruiting
First Posted : September 10, 2018
Last Update Posted : February 7, 2019
Sponsor:
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

Tracking Information
First Submitted Date  ICMJE July 25, 2018
First Posted Date  ICMJE September 10, 2018
Last Update Posted Date February 7, 2019
Actual Study Start Date  ICMJE March 1, 2018
Estimated Primary Completion Date July 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
Change in the glomerular filtration rate [ Time Frame: The measurements will be done baseline and every six months up to 24 months. ]
Glomerular filtration rate (GFR) will be calculated based in Cystatin C level Grubb's equations. Serum Cystatin C will be measured by ELISA
Change History Complete list of historical versions of study NCT03664414 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2018)
  • 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)
  • 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)
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2018)
  • Change in oxidative stress marker. [ Time Frame: Change is assessed baseline, 6 months, 12 months, 18 months and 24 months. ]
    Vitamin C will be measured by HPLC as a marker of oxidative stress.
  • Change in fibrosis markers. [ Time Frame: Change is assessed baseline, 6 months, 12 months, 18 months and 24 months. ]
    This outcome will be assessed in laboratory assay by the measurement of Brain natriuretic peptide by ELISA; and through the measurement of the left ventricle mass measured by M-mode and two-dimensional echocardiography.
  • 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.
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pentoxifylline Effect in Patients With Diabetic Nephropathy.(PENFOSIDINE STUDY)
Official Title  ICMJE Pentoxifylline Effect on Renal Function, Oxidative Stress, Inflammation, and Fibrosis Markers, and Quality of Life in Patients With Diabetic Nephropathy
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE 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
Condition  ICMJE
  • Chronic Kidney Disease stage3 and 4
  • Type 2 Diabetes Mellitus
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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.
    Intervention: Drug: pentoxifylline
  • 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.
    Intervention: Drug: pentoxifylline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 6, 2018)
196
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date July 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 30 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
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
Listed Location Countries  ICMJE Mexico
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03664414
Other Study ID Numbers  ICMJE CNIC-2015-785-065
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Supporting Materials: 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.
Responsible Party Maria Eugenia Galván Plata, Coordinación de Investigación en Salud, Mexico
Study Sponsor  ICMJE Maria Eugenia Galván Plata
Collaborators  ICMJE
  • 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  ICMJE
Principal Investigator: Oliva Mejía-Rodríguez, PhD CIBIMI IMSS
PRS Account Coordinación de Investigación en Salud, Mexico
Verification Date February 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP