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Optimal Management of HIV Infected Adults at Risk for Kidney Complications in Nigeria

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03201939
Recruitment Status : Not yet recruiting
First Posted : June 28, 2017
Last Update Posted : January 13, 2021
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Aminu Kano Teaching Hospital
SAIC-Frederick, Inc.
Information provided by (Responsible Party):
C. William Wester, Vanderbilt University Medical Center

Brief Summary:
In this study, the Investigators plan to determine the optimal means to prevent or slow the progression of kidney disease among genetically at-risk northern Nigerian HIV-infected adults. Based on data from studies of diabetic kidney disease that used medications that block the renin angiotensin aldosterone system (RAAS), we plan to evaluate whether or not RAAS inhibition (using a widely available medication that blocks RAAS) in HIV-infected adults produces similarly promising results.

Condition or disease Intervention/treatment Phase
HIV/AIDS Albuminuria Kidney Diseases Genetic Predisposition Drug: Lisinopril Other: Placebo Oral Tablet Phase 2

Detailed Description:

Individuals of African descent have a much higher risk for glomerular diseases. Specifically, there are two risk variants in the chromosome 22 APOL1 gene (G1/G2) and persons possessing 2 copies of these risk variants (G1/G1, G1/G2, or G2/G2), referred to as the high-risk (HR) genotype, are at high risk for non-diabetic kidney disease. Kopp et al. have shown that the APOL1 high-risk genotype confers sizeable odds ratios (OR) for FSGS (OR = 17), HIVAN (OR = 29 in the US; 89 in S. Africa), and hypertension-attributed end stage kidney disease (OR = 7). The presence of these risk variants is highest in West Africa, and specifically in Nigeria among persons of Hausa, Fulani, and Igbo descent. In the setting of untreated HIV infection, we have estimated that ~50% of individuals carrying the APOL1 HR genotype will develop chronic kidney disease (CKD). However, there is limited availability of dialysis and kidney transplantation in Nigeria, and most individuals will die soon after developing ESKD. Markers of kidney disease include microalbuminuria, proteinuria, and/or reduced estimated glomerular filtration rate (eGFR). All 3 have been associated with increased mortality in HIV+ adults. Increased urinary albumin excretion has diagnostic and prognostic value in the identification and confirmation of renal disease, and changes in albuminuria can be useful in assessing treatment efficacy as well as disease progression. Microalbuminuria, i.e., urine albumin to creatinine ratio (uACR) in the 30-300 mg/g range, is likely the earliest stage of CKD, analogous to diabetic microalbuminuria. The renin-angiotensin aldosterone system (RAAS) is the central player in the pathophysiology of CKD and blocking RAAS with angiotensin converting enzyme inhibitors (ACEi) is a well-recognized strategy to slow or halt renal disease progression in diabetics with CKD. To determine whether the presence of APOL1 HR genotype alters or predicts responsiveness to conventional therapy and if the addition of an ACEi to standard antiretroviral therapy (ART) reduces the risk for renal complications among West African adults, we will screen 2,600 HIV+ ART-experienced adults; to conduct the following Specific Aims:

  1. To determine the prevalence of APOL1 renal risk variants and assess whether APOL1 HR status correlates with prevalent albuminuria, eGFR, and/or prevalent CKD in a West African population.
  2. To assess whether RAAS inhibition (with the ACEi lisinopril) in addition to ART, compared to the existing standard-of-care (SOC), will significantly reduce the incidence of additional kidney disease manifestations. We will randomize ART-experienced (6+ months) adults with prevalent microalbuminuria (uACR 30-300 mg/g) and an eGFR of > 30 ml/min/1.73m2 to lisinopril (n=140) vs. SOC (n=140); and
  3. To determine whether the APOL1 HR genotype is associated with worse longitudinal renal outcomes in Nigerians with prevalent albuminuria.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 280 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blind, placebo-controlled RCT
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind, placebo-controlled RCT
Primary Purpose: Treatment
Official Title: Optimal Management of HIV Infected Adults at Risk for Kidney Complications in Nigeria
Estimated Study Start Date : January 30, 2021
Estimated Primary Completion Date : February 28, 2023
Estimated Study Completion Date : August 30, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Lisinopril

Arm Intervention/treatment
Active Comparator: Active Medication (Intervention arm)
ACE-inhibitor lisinopril
Drug: Lisinopril
ACE-inhibitor (lisinopril)(intervention arm
Other Name: Intervention arm

Placebo Comparator: Placebo comparator (Control arm)
Matched placebo
Other: Placebo Oral Tablet
Comparator placebo (control arm)
Other Name: Control arm

Primary Outcome Measures :
  1. Regression from microalbuminuria (uACR 30-300) to normoalbuminuria (uACR < 30 mg/g) by study arm [ Time Frame: 2 years ]
    Reduction/improvement in degree/grade of albuminuria

  2. Progression from microalbuminuria (uACR 30-300) to macroalbuminuria (uACR > 300 mg/g) by study arm [ Time Frame: 2 years ]
    Progression/worsening in degree/grade of albuminuria

  3. Mean change in urinary albumin to creatinine ratio (uACR) [ Time Frame: 2 years ]
    Mean change in urinary albumin excretion

Secondary Outcome Measures :
  1. Doubling of serum creatinine from baseline [ Time Frame: 2 years ]
    Worsening renal function (as measured by serum creatinine)

  2. All-cause mortality [ Time Frame: 2 years ]

  3. Proportion experiencing a 40% decline in eGFR [ Time Frame: 2 years ]
    Proportion with 40% decline in eGFR (measured using CKD-EPI-Cr-CyC equation)

  4. Mean change in eGFR over time [ Time Frame: 2 years ]
    Mean change in eGFR (measured using CKD-EPI-Cr-CyC equation)

  5. Change in clinical/performance status as ascertained via World Health Organization Quality of Life HIV (WHOQOL-HIV) scale [ Time Frame: baseline, 1 year, 2 years ]
    WHOQOL-HIV scale evaluates quality of life based on physical, psychological, social, environmental, and spiritual domains, as well as level of independence. We will use the 31-question version, with each question rated on a 5-point Likert scale. Scores of questions within each domain are averaged to get domain score, and final score is mean of domain scores multiplied by 4. Final score ranges from 4 to 20, with 20 being optimal.

  6. Change in clinical/performance status as ascertained via Karnofsky Performance Score [ Time Frame: baseline, 1 year, 2 years ]
    Karnofsky Performance Score measures change in clinical/performance status with values ranging from 0 to 100, where 100 is perfect health and 0 is death.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Both males and females eligible
Accepts Healthy Volunteers:   Yes

Inclusion criteria:

  • Participated in Study Aim 1
  • 18-70 years of age
  • HIV-positive (as documented by HIV-1 ELISA testing)
  • On ART for a minimum of six (6) months AND having a suppressed plasma viral load result (< 20 copies/mL) within the past 6 months
  • Average uACR between 30-300 mg/g (based on 2 uACRs [first morning voids], with the second obtained 4-8 weeks after the first specimen)(NOTE: All aim 1 screened patients having a uACR value > 300 mg/g will undergo urine dipstick analysis for aim 2 eligibility, and if their urine dipstick results reveals ≥ 2+ protein, then they will be considered ineligible (no additional uACR testing will be necessary to determine eligibility)
  • eGFR = >60 ml/min/1.73m2 (using CKD-EPI-Cr-CyC equation) AND
  • If female, non-pregnant (documentation of negative urine pregnancy test) and not breastfeeding/lactating

Exclusion criteria:

  • Pregnant or currently breastfeeding
  • eGFR of <60 ml/min/1.73m2 (using CKD-EPI-Cr-CyC equation)
  • Average uACR > 300 mg/g (based on 2 uACRs [first morning voids], with the second obtained 4-8 weeks after the first specimen)
  • K+ >5.0 meEq/L or reasons to be concerned about hyperkalemia
  • Known history of Diabetes diabetes mellitus (would qualify for treatment with an ACEi/ARB)
  • Poorly controlled hypertension (≥3 BP readings >160/110 in past 3 6 months)
  • Known history of Congestive congestive heart failure (chronic)
  • Average uACR (calculated on values obtained from 2 successive measures 4-8 weeks apart) of < 30 mg/g OR > 300 mg/g
  • Relative symptomatic hypotension (BP <90/60)
  • Currently receiving an ACEi and/or ARB; OR
  • Lack of suitability as a study candidate (i.e. active substance use disorder, active use of potentially nephrotoxic medication(s) (i.e. traditional medicines, etc.) and/or consistent alcohol, drug, and/or traditional medication use, and/or history of poor compliance (i.e. multiple missed scheduled clinic appointments, etc.)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03201939

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Contact: C. William Wester, MD, MPH +001-615-875-0145
Contact: Donna J. Ingles, MS, MPH +001-615-343-3555

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Aminu Kano Teaching Hospital
Kano, Nigeria
Contact: Baba M Musa, MBBS, MPH    +234-803-347-2311   
Contact: Faisal S. Danikshiya, MBBS    234-806-129-7871   
Sponsors and Collaborators
Vanderbilt University Medical Center
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Aminu Kano Teaching Hospital
SAIC-Frederick, Inc.
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Principal Investigator: C. William Wester, MD, MPH Vanderbilt University Medical Center
Principal Investigator: Muktar H. Aliyu, MD, DrPH Vanderbilt University Medical Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: C. William Wester, Associate Professor of Medicine, Vanderbilt University Medical Center Identifier: NCT03201939    
Other Study ID Numbers: Vanderbilt_University MC
U01DK112271 ( U.S. NIH Grant/Contract )
First Posted: June 28, 2017    Key Record Dates
Last Update Posted: January 13, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Investigative team will work with study biostatisticians, DSMB members, and collaborators to release analysis scripts (with publications) and devise an IPD sharing plan at/near study completion.
Time Frame: Approximately 6 months after collection of the final patient data.
Access Criteria: Deidentified data will be available after the conclusion of the study for investigators who are approved by the trial leadership at VUMC, AKTH, and NIH.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by C. William Wester, Vanderbilt University Medical Center:
sub-Saharan Africa
Kidney disease
Genetic risk
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Kidney Diseases
Disease Susceptibility
Genetic Predisposition to Disease
Urologic Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Urination Disorders
Urological Manifestations
Disease Attributes
Pathologic Processes
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents
Cardiotonic Agents
Protective Agents
Physiological Effects of Drugs