<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03019848</url>
  </required_header>
  <id_info>
    <org_study_id>INC.12-793</org_study_id>
    <nct_id>NCT03019848</nct_id>
  </id_info>
  <brief_title>Effect of Oral Supplementation With Curcumin in Patients With Proteinuric Diabetic Kidney Disease</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Instituto Nacional de Cardiologia Ignacio Chavez</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Instituto Nacional de Cardiologia Ignacio Chavez</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine if the oral supplementation with curcumin reduces&#xD;
      proteinuria, improves the redox and pro-inflammatory state in patients with chronic kidney&#xD;
      disease associated to Diabetes mellitus.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Diabetic Kidney Disease (DKD) represents the fist cause of end-stage kidney disease in Mexico&#xD;
      and the world, and it is characterized by the presence of hyperfiltration, glomerular&#xD;
      hypertrophy, tubular albuminuria and mesangial matrix expansion, mainly by the oxidative&#xD;
      stress and the pro-inflammatory state.&#xD;
&#xD;
      Current treatments are limited on controlling proteinuria and delay progression of the&#xD;
      disease, but even with an optimal management, a significant number of patient progress to&#xD;
      end-stage renal disease.&#xD;
&#xD;
      Curcumin, found in the extracts of the rhizome of the plant Curcuma longa L., has a wide&#xD;
      spectrum of biological and pharmacological activities, such as anti-oxidant,&#xD;
      anti-inflammatory, anti-carcinogenic and anti-diabetic effects. It has the capacity to act&#xD;
      directly with highly reactive oxygen species, induce the expression of various cytoprotective&#xD;
      proteins through Keap1/Nrf2/ARE pathway and reducing inflammatory transcription factors such&#xD;
      as NF-κB and TNF-α.&#xD;
&#xD;
      Curcumin could be an adjuvant treatment in the management of DKC due to his pleiotropic&#xD;
      nature, low cost and few side effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>May 2016</start_date>
  <completion_date type="Anticipated">May 2017</completion_date>
  <primary_completion_date type="Anticipated">May 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Urine protein excretion</measure>
    <time_frame>24 weeks</time_frame>
    <description>Quantify proteinuria and adjust based in creatinuria, before and after the treatment. ( Units: g/g).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Free radical scavenging activity</measure>
    <time_frame>6 months</time_frame>
    <description>Free radical scavenging activity in plasma using DPPH, a purple-colored stable free radical is reduced to the yellow-colored diphenyl picryl-hydrazine, and the absorbance will be measure at 518 nm.&#xD;
The results were expressed as percentage of DPPH inhibition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Malondialdehyde (MDA)</measure>
    <time_frame>6 months</time_frame>
    <description>Malondialdehyde (MDA) in plasma. We will measure the reaction with 1-methyl-2- phenylindole at 586 nm, using a standard curve of tetrame- thoxypropane.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proinflammatory status</measure>
    <time_frame>6 months</time_frame>
    <description>Enzyme-linked immunoassay (ELISA) will be use to the measurement of serum TGF-b, IL-10, IL-6 and TNF-a.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Proteinuria</condition>
  <arm_group>
    <arm_group_label>Curcumin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each patient of this group will receive 1.67 grams of curcumin ( 7 capsules of 231 mg) divided in 3 doses daily for 6 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>The control group will receive 7-capsules/ day identical in color and size, containing placebo for 6 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Curcumin</intervention_name>
    <arm_group_label>Curcumin</arm_group_label>
    <other_name>Tumeric</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of Diabetes Mellitus type 2 and proteinuric kidney disease with 1000 mg of&#xD;
             more proteins in daily recollection&#xD;
&#xD;
          -  Glomerular filtration rate between 15-60 mL/min/ 1.73 m2 calculated by CKD-EPI&#xD;
&#xD;
          -  Patients taking Angiotensin II Receptor Blocker or ACE inhibitors&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Renal replacement therapy&#xD;
&#xD;
          -  Autoimmune disease or malignancy&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Hepatic damage&#xD;
&#xD;
          -  Congestive heart failure classification III or IV (NYHA)&#xD;
&#xD;
          -  History of organ transplantation&#xD;
&#xD;
          -  History of chemotherapy or immunosuppression within 2 years prior to screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Magdalena Madero, MD</last_name>
    <phone>55-5573-2911</phone>
    <phone_ext>1262</phone_ext>
    <email>madero.magdalena@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Alfonso Gindl, MD</last_name>
    <phone>55-5573-2911</phone>
    <phone_ext>1262</phone_ext>
    <email>alfonsogindl@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Instituto Nacional de Cardiologia Ignacio Chávez</name>
      <address>
        <city>Mexico City</city>
        <zip>14080</zip>
        <country>Mexico</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Mexico</country>
  </location_countries>
  <reference>
    <citation>National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266. No abstract available.</citation>
    <PMID>11904577</PMID>
  </reference>
  <reference>
    <citation>de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004 Jun;65(6):2309-20. doi: 10.1111/j.1523-1755.2004.00653.x.</citation>
    <PMID>15149345</PMID>
  </reference>
  <reference>
    <citation>Trujillo J, Chirino YI, Molina-Jijon E, Anderica-Romero AC, Tapia E, Pedraza-Chaverri J. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol. 2013 Sep 17;1(1):448-56. doi: 10.1016/j.redox.2013.09.003.</citation>
    <PMID>24191240</PMID>
  </reference>
  <reference>
    <citation>Khajehdehi P, Pakfetrat M, Javidnia K, Azad F, Malekmakan L, Nasab MH, Dehghanzadeh G. Oral supplementation of turmeric attenuates proteinuria, transforming growth factor-beta and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: a randomized, double-blind and placebo-controlled study. Scand J Urol Nephrol. 2011 Nov;45(5):365-70. doi: 10.3109/00365599.2011.585622. Epub 2011 May 31.</citation>
    <PMID>21627399</PMID>
  </reference>
  <reference>
    <citation>Jimenez-Osorio AS, Garcia-Nino WR, Gonzalez-Reyes S, Alvarez-Mejia AE, Guerra-Leon S, Salazar-Segovia J, Falcon I, Montes de Oca-Solano H, Madero M, Pedraza-Chaverri J. The Effect of Dietary Supplementation With Curcumin on Redox Status and Nrf2 Activation in Patients With Nondiabetic or Diabetic Proteinuric Chronic Kidney Disease: A Pilot Study. J Ren Nutr. 2016 Jul;26(4):237-44. doi: 10.1053/j.jrn.2016.01.013. Epub 2016 Feb 22.</citation>
    <PMID>26915483</PMID>
  </reference>
  <verification_date>September 2016</verification_date>
  <study_first_submitted>September 12, 2016</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 13, 2017</study_first_posted>
  <last_update_submitted>January 11, 2017</last_update_submitted>
  <last_update_submitted_qc>January 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Instituto Nacional de Cardiologia Ignacio Chavez</investigator_affiliation>
    <investigator_full_name>Magdalena Madero</investigator_full_name>
    <investigator_title>MD, Chief of the Nephrology Department</investigator_title>
  </responsible_party>
  <keyword>Redox and pro-inflammatory status</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Proteinuria</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Curcumin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03019848
org study id: INC.12-793
nct id: NCT03019848
lead sponsor: 
has dmc: No
The purpose of this study is to determine if the oral supplementation with curcumin reduces
      proteinuria, improves the redox and pro-inflammatory state in patients with chronic kidney
      disease associated to Diabetes mellitus.
Diabetic Kidney Disease (DKD) represents the fist cause of end-stage kidney disease in Mexico
      and the world, and it is characterized by the presence of hyperfiltration, glomerular
      hypertrophy, tubular albuminuria and mesangial matrix expansion, mainly by the oxidative
      stress and the pro-inflammatory state.

      Current treatments are limited on controlling proteinuria and delay progression of the
      disease, but even with an optimal management, a significant number of patient progress to
      end-stage renal disease.

      Curcumin, found in the extracts of the rhizome of the plant Curcuma longa L., has a wide
      spectrum of biological and pharmacological activities, such as anti-oxidant,
      anti-inflammatory, anti-carcinogenic and anti-diabetic effects. It has the capacity to act
      directly with highly reactive oxygen species, induce the expression of various cytoprotective
      proteins through Keap1/Nrf2/ARE pathway and reducing inflammatory transcription factors such
      as NF-κB and TNF-α.

      Curcumin could be an adjuvant treatment in the management of DKC due to his pleiotropic
      nature, low cost and few side effects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Urine protein excretion
time frame: 24 weeks
description: Quantify proteinuria and adjust based in creatinuria, before and after the treatment. ( Units: g/g).
measure: Free radical scavenging activity
time frame: 6 months
description: Free radical scavenging activity in plasma using DPPH, a purple-colored stable free radical is reduced to the yellow-colored diphenyl picryl-hydrazine, and the absorbance will be measure at 518 nm.
The results were expressed as percentage of DPPH inhibition.
measure: Malondialdehyde (MDA)
time frame: 6 months
description: Malondialdehyde (MDA) in plasma. We will measure the reaction with 1-methyl-2- phenylindole at 586 nm, using a standard curve of tetrame- thoxypropane.
measure: Proinflammatory status
time frame: 6 months
description: Enzyme-linked immunoassay (ELISA) will be use to the measurement of serum TGF-b, IL-10, IL-6 and TNF-a.
arm group label: Curcumin
arm group type: Experimental
description: Each patient of this group will receive 1.67 grams of curcumin ( 7 capsules of 231 mg) divided in 3 doses daily for 6 months.
arm group label: Placebo
arm group type: Placebo Comparator
description: The control group will receive 7-capsules/ day identical in color and size, containing placebo for 6 months.
intervention type: Dietary Supplement
intervention name: Curcumin
arm group label: Curcumin
other name: Tumeric
intervention type: Other
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Magdalena Madero, MD
phone: 55-5573-2911
phone ext: 1262
email: madero.magdalena@gmail.com
last name: Alfonso Gindl, MD
phone: 55-5573-2911
phone ext: 1262
email: alfonsogindl@hotmail.com
facility: 
status: Recruiting
country: Mexico
citation: National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266. No abstract available.
PMID: 11904577
citation: de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, Snapinn S, Cooper ME, Mitch WE, Brenner BM. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004 Jun;65(6):2309-20. doi: 10.1111/j.1523-1755.2004.00653.x.
PMID: 15149345
citation: Trujillo J, Chirino YI, Molina-Jijon E, Anderica-Romero AC, Tapia E, Pedraza-Chaverri J. Renoprotective effect of the antioxidant curcumin: Recent findings. Redox Biol. 2013 Sep 17;1(1):448-56. doi: 10.1016/j.redox.2013.09.003.
PMID: 24191240
citation: Khajehdehi P, Pakfetrat M, Javidnia K, Azad F, Malekmakan L, Nasab MH, Dehghanzadeh G. Oral supplementation of turmeric attenuates proteinuria, transforming growth factor-beta and interleukin-8 levels in patients with overt type 2 diabetic nephropathy: a randomized, double-blind and placebo-controlled study. Scand J Urol Nephrol. 2011 Nov;45(5):365-70. doi: 10.3109/00365599.2011.585622. Epub 2011 May 31.
PMID: 21627399
citation: Jimenez-Osorio AS, Garcia-Nino WR, Gonzalez-Reyes S, Alvarez-Mejia AE, Guerra-Leon S, Salazar-Segovia J, Falcon I, Montes de Oca-Solano H, Madero M, Pedraza-Chaverri J. The Effect of Dietary Supplementation With Curcumin on Redox Status and Nrf2 Activation in Patients With Nondiabetic or Diabetic Proteinuric Chronic Kidney Disease: A Pilot Study. J Ren Nutr. 2016 Jul;26(4):237-44. doi: 10.1053/j.jrn.2016.01.013. Epub 2016 Feb 22.
PMID: 26915483
responsible party type: Principal Investigator
investigator affiliation: Instituto Nacional de Cardiologia Ignacio Chavez
investigator full name: Magdalena Madero
investigator title: MD, Chief of the Nephrology Department
mesh term: Proteinuria
mesh term: Curcumin