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

NCT03201939 | Terminated Phase 2 Results DMC

• 2 other identifiers: Vanderbilt_University MCU01DK112271
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV/AIDS; Albuminuria; Kidney Diseases; Genetic Predisposition

Keywords

HIV/AIDS; sub-Saharan Africa; Kidney disease; Albuminuria; Genetic risk

Outcome Measures

Primary Outcomes (3)

• Regression From Microalbuminuria (uACR 30-300) to Normoalbuminuria (uACR < 30 mg/g) by Study Arm

  Proportion of study participants regressing from microalbuminuria (uACR 30-300) to normoalbuminuria (uACR \< 30 mg/g) by study arm

  2 years

• Progression From Microalbuminuria (uACR 30-300) to Macroalbuminuria (uACR > 300 mg/g) by Study Arm

  Proportion of study participants progressing from microalbuminuria (uACR 30-300) to macroalbuminuria (uACR \> 300 mg/g) by study arm

  2 years

• Mean Change in Urinary Albumin to Creatinine Ratio (uACR)

  Mean change in urinary albumin to creatinine ratio (uACR) among study participants at study timepoints by study arm

  2 years

Secondary Outcomes (6)

• Doubling of Serum Creatinine From Baseline

  2 years

• All-cause Mortality

  2 years

• Proportion Experiencing a 40% Decline in eGFR

  2 years

• Mean Change in eGFR Over Time

  2 years

• Change in Clinical/Performance Status as Ascertained Via World Health Organization Quality of Life HIV (WHOQOL-HIV) Scale

  Baseline, 1 year, 2 years

Study Arms (2)

Active Medication (Intervention arm)

ACTIVE COMPARATOR

ACE-inhibitor lisinopril

Drug: Lisinopril

Placebo comparator (Control arm)

PLACEBO COMPARATOR

Matched placebo

Other: Placebo Oral Tablet

Interventions

Lisinopril DRUG

ACE-inhibitor (lisinopril)(intervention arm

Also known as: Intervention arm

Active Medication (Intervention arm)

Placebo Oral Tablet OTHER

Comparator placebo (control arm)

Also known as: Control arm

Placebo comparator (Control arm)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Gender Eligibility Details: Both males and females eligible
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participated in Study Aim 1
• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Aminu Kano Teaching Hospital: collaborator
• SAIC-Frederick, Inc.: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Aminu Kano Teaching Hospital

Kano, Nigeria

Location

Related Publications (2)

• Wudil UJ, Aliyu MH, Prigmore HL, Ingles DJ, Ahonkhai AA, Musa BM, Muhammad H, Sani MU, Nalado AM, Abdu A, Abdussalam K, Shepherd BE, Dankishiya FS, Burgner AM, Ikizler TA, Wyatt CM, Kopp JB, Kimmel PL, Winkler CA, Wester CW. Apolipoprotein-1 risk variants and associated kidney phenotypes in an adult HIV cohort in Nigeria. Kidney Int. 2021 Jul;100(1):146-154. doi: 10.1016/j.kint.2021.03.038. Epub 2021 Apr 24.

  PMID: 33901548 BACKGROUND

• Aliyu MH, Wudil UJ, Ingles DJ, Shepherd BE, Gong W, Musa BM, Muhammad H, Sani MU, Abdu A, Nalado AM, Atanda A, Ahonkhai AA, Ikizler TA, Winkler CA, Kopp JB, Kimmel PL, Wester CW. Optimal management of HIV- positive adults at risk for kidney disease in Nigeria (Renal Risk Reduction "R3" Trial): protocol and study design. Trials. 2019 Jun 10;20(1):341. doi: 10.1186/s13063-019-3436-y.

  PMID: 31182139 BACKGROUND

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Albuminuria; Kidney Diseases; Genetic Predisposition to Disease

Interventions

Lisinopril

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Disease Susceptibility; Disease Attributes; Pathologic Processes

Intervention Hierarchy (Ancestors)

Dipeptides; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

The primary limitation of this study was laboratory quality control (QC) issues. While all QC concerns were addressed, the time required to resolve them led to a delay in the study. Although the Data and Safety Monitoring Board (DSMB) approved the study's re-opening, the extended resolution period resulted in insufficient follow-up time to complete the study as originally planned

Results Point of Contact

• Title: C. William Wester
• Organization: Vanderbilt University Medical Center

william.wester@vumc.org

6158750145

Study Officials

• C. William Wester, MD, MPH

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Muktar H. Aliyu, MD, DrPH

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, placebo-controlled RCT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Model Details: Double-blind, placebo-controlled RCT

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: June 28, 2017
• Study Start: April 1, 2021
• Primary Completion: November 30, 2021
• Study Completion: February 1, 2025
• Last Updated: June 26, 2025
• Results First Posted: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

NG (1)