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Tenofovir Renal Toxicity and Glomerular Filtration Rate (GFR) Validation

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2011 by The HIV Netherlands Australia Thailand Research Collaboration.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Chulalongkorn University
Kirby Institute
Information provided by:
The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier:
NCT01138241
First received: June 4, 2010
Last updated: February 3, 2011
Last verified: February 2011
History of Changes
  Purpose

To assess and validate equation eGFR in HIV-infected subjects and -uninfected Thai patients


Condition Intervention
Renal Function
HIV Infection
 Other: Tc99mDTPA renal clearance

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Incidence and Predictor of TDF Associated Nephrotoxicity and Pharmacokinetic of TDF in HIV-1 Infected Thai Patients: A Sub-study of HIV-NAT 006 Long Term Cohort

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by The HIV Netherlands Australia Thailand Research Collaboration:

Secondary Outcome Measures:
  • eGFR by C-G formula, MDRD, CKD-EPI [ Time Frame: June 2010 to May 2011 ] [ Designated as safety issue: No ]
    The eGFR values will be calculated by the re-expressed IDMS traceable MDRD, C-G, and CKD-EPI.

  • GFR by cystatin C [ Time Frame: June 2010 to May 2011 ] [ Designated as safety issue: No ]
    Serum for cystatin C levels will be collected at the time of serum creatinine collection. Cystatin C will be measured by quantitative sandwich enzyme immunoassay. GFR will be estimated from the cystatin C measurement using the following equation18: Cystatin C GFR=86.7/cystatin-4.2.

  • GFR by urine 24 hours [ Time Frame: June 2010 to May 2011 ] [ Designated as safety issue: No ]
    Urine will be collected over a 24-hour period. Verbal and written instructions for collecting urine at home will be given to the patients. Containers (5litres) will be provided for all patients. Creatinine clearance (CrCl) will be calculated using the following equation: CrCl= Urine Cr/Serum cr xQu ; where Qu is the urine volume divided by the time of the actual collection. CrCl estimates will be adjusted for BSA.

  • TDF plasma levels [ Time Frame: June 2010 to May 2011 ] [ Designated as safety issue: No ]
    TDF plasma concentrations are assessed by using a validated high-performance liquid chromatography (HPLC)-mass method. Blood will be collected in lithium-heparin or sodium-heparin tube at mid dose (10-12 hr post dose of TDF). The exact times of sampling will be recorded in the case report forms. Plasma will be stored at - 20 C until analysis and will be transferred to - 80 C for long term storage at HIV-NAT laboratory. Blood for pharmacokinetic study will be obtained at HIV-NAT. The TDF drug level will be determined by HPLC method at the HIV-NAT PK laboratory in Bangkok.


Biospecimen Retention:   Samples With DNA

PBMC collection


Estimated Enrollment: 700
Study Start Date: March 2010
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
1
ARV experience (TDF based HAART)
 Other: Tc99mDTPA renal clearance

Tc99mDTPA renal clearance only for 200 patients

  1. Plasma and urine 24 hr for creatinin, glucose, Creatinin clearance, Phosphatemia, uric acid, HCO3, protein, Microalbuminuria, ß2- microglobulinuria
  2. serum creatinine prior and during TDF
  3. TDF plasma levels ( only TDF use) using a validated high-performance liquid chromatography (HPLC)-mass method and stored PBMC for intracellular TDF levels
  4. stored samples (PBMC) for pharmacogenomic study of transporter gene ie Organic Acid Transporter (OAT)
  5. serum for cystanin C ( stored sample prior taking ARV and present time)
  6. intensive 24 hours pharmacokinetic study of TDF in 20 patients
2
ARV experience (non TDF based ART)
 Other: Tc99mDTPA renal clearance

Tc99mDTPA renal clearance only for 200 patients

  1. Plasma and urine 24 hr for creatinin, glucose, Creatinin clearance, Phosphatemia, uric acid, HCO3, protein, Microalbuminuria, ß2- microglobulinuria
  2. serum creatinine prior and during TDF
  3. TDF plasma levels ( only TDF use) using a validated high-performance liquid chromatography (HPLC)-mass method and stored PBMC for intracellular TDF levels
  4. stored samples (PBMC) for pharmacogenomic study of transporter gene ie Organic Acid Transporter (OAT)
  5. serum for cystanin C ( stored sample prior taking ARV and present time)
  6. intensive 24 hours pharmacokinetic study of TDF in 20 patients
3
ARV Naive
 Other: Tc99mDTPA renal clearance

Tc99mDTPA renal clearance only for 200 patients

  1. Plasma and urine 24 hr for creatinin, glucose, Creatinin clearance, Phosphatemia, uric acid, HCO3, protein, Microalbuminuria, ß2- microglobulinuria
  2. serum creatinine prior and during TDF
  3. TDF plasma levels ( only TDF use) using a validated high-performance liquid chromatography (HPLC)-mass method and stored PBMC for intracellular TDF levels
  4. stored samples (PBMC) for pharmacogenomic study of transporter gene ie Organic Acid Transporter (OAT)
  5. serum for cystanin C ( stored sample prior taking ARV and present time)
  6. intensive 24 hours pharmacokinetic study of TDF in 20 patients

Detailed Description:

With significant reductions in mortality and risk of progression to AIDS with antiretroviral therapy (ART), complications of long-standing HIV infection and treatment, including renal disease, have become increasingly important. Aging, concomitant metabolic diseases, and use of potentially nephrotoxic ART lead to higher risk for renal disease in HIV-infected persons.WHO encourage TDF as first line ARV regimen. The data on TDF related renal toxicity in Asian population is limited.

For this cohort, we plan to look at these topics:

  1. proximal tubular dysfunction between TDF and non-TDF user
  2. incidence and predictor of TDF related renal toxicity
  3. TDF plasma concentrations
  4. Pharmacokinetic of TDF when used with boosted DRV, boosted ATV, and boosted LPV in Thai population
  5. Bone density and vitamin D in patients with and without hypophosphatemia.
  6. Pharmacogenomic of TDF in Thai population
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

HIV-NAT 006 participants (TDF +non TDF)and ARV naive population

For TDF group, on TDF > 3 months HIV/HBV co-infected patients from COLD (Liver disease and HIV/HBV coinfection in the era of HAART) and TDF surveillance study

Criteria

Inclusion Criteria:

  1. > 18 years old.
  2. HIV RNA < 50 copies/ml (For ART-experienced group only).

Exclusion Criteria:

  1. a history of Tc-99m DTPA allergy,
  2. malnutrition (BMI <18m2),
  3. amputation,
  4. bed-ridden,
  5. currently taking cotrimoxazole or cimetidine,
  6. acute deterioration of renal function within the last 3 months,
  7. serum creatinine > 1.5 mg/dl, or
  8. pregnant/lactating.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01138241

Contacts
Contact: Anchalee Avihingsanon, MD 662-652-3040 ext 107 anchalee.a@hivnat.org
Contact: Supaporn Plengsuma, RN 662-652-3040 ext 165 supaporn.p@hivnat.org

Locations
Thailand
HIV-NAT, Thai Red Cross AIDS Research Centre Recruiting
Bangkok, Thailand, 10330
Contact: Anchalee Avihingsanon, MD     662-652-3040 ext 107     anchalee.a@hivnat.org    
Contact: Supaporn Plengsuma, RN     662-652-3040 ext 165     supaporn.p@hivnat.org    
Sub-Investigator: Tawatchai Chaiwatanarat, MD            
Sub-Investigator: Yingyos Avihingsanon, MD            
Sub-Investigator: Jintanat Ananworanich, MD, PhD            
Sponsors and Collaborators
The HIV Netherlands Australia Thailand Research Collaboration
Chulalongkorn University
Kirby Institute
Investigators
Principal Investigator: Praphan Phanuphak, MD, PhD HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
Principal Investigator: Kearkiat Praditpornsilpa, MD Renal division, Faculty of Medicine, Chulalongkorn University
  More Information

Additional Information:
HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Praphan Phanuphak, HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
ClinicalTrials.gov Identifier: NCT01138241     History of Changes
Other Study ID Numbers: HIV-NAT 114
Study First Received: June 4, 2010
Last Updated: February 3, 2011
Health Authority: Thailand: Ethical Committee

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:
HIV
Chronic kidney disease
Glomerular Filtration Rate (GFR)
Tenofovir
Serum creatinine (sCr)
24 hr urine creatinine clearance
 Serum Cystatin C[40]
Modification of Diet in Renal Disease (MDRD)
Cockcroft Gault Equation
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
99mTc-diethylenetriaminepentaacetic acid (Tc-99m DTPA) scan
Validate which renal function assessments can accurately detect GFR and assess the effect of TDF concentration on renal function

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Pentetic Acid
Edetic Acid
Tenofovir
Chelating Agents
 Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antidotes
Protective Agents
Physiological Effects of Drugs
Iron Chelating Agents
Anticoagulants
Hematologic Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 16, 2013