Management of Cardiovascular Disease in Kidney Disease (MaCK) Study

NCT03636152 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: CARB-013-17FICX001661A
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Cardiovascular disease (CVD) is the largest concerns for patients with Chronic kidney disease (CKD). At present time the investigators do not have proven effective strategies to reduce high CVD related deaths in CKD. This study assesses a novel therapy (hydroxychloroquine, HCQ) for the treatment of CVD in patients with CKD. This is the first human proof-of-concept study and is planned to be conducted among US Veterans, who suffer from both CKD and CVD at a disproportionately greater rates. The outcome of this study has the potential to provide an entirely new line of therapy for the treatment of CVD in CKD.

Conditions

Chronic Kidney Disease; Cardiovascular Disease; Inflammation; Atherosclerosis; Aortic Stiffness

Keywords

chronic kidney disease; cardiovascular disease; Inflammation; Atherosclerosis; Vascular stiffness

Outcome Measures

Primary Outcomes (1)

• Total Plaque Volume (TPV), Carotid

  Measurements of Carotid TPV at enrollment and serially over 18th months

  18 months

Secondary Outcomes (2)

• High Sensitivity C-Reactive Protein (hsCRP)

  18 months

• Aortic Pulse Wave Velocity (APWV)

  18 months

Study Arms (2)

Hydroxychloroquine (HCQ) Group

ACTIVE COMPARATOR

These patients will receive HCQ for 18 months

Procedure: MRI carotid; Procedure: APWV; Drug: Hydroxychloroquine

Placebo Group

PLACEBO COMPARATOR

These patients will receive a matching placebo for 18 months

Procedure: MRI carotid; Procedure: APWV; Drug: Matching Placebo

Interventions

MRI carotid PROCEDURE

To assess the carotid atherosclerotic plaques

Also known as: Carotid MRI

Hydroxychloroquine (HCQ) Group; Placebo Group

APWV PROCEDURE

Doppler measurement of the APWV

Also known as: aortic pulse wave velocity, pulse wave velocity, vascular stiffness

Hydroxychloroquine (HCQ) Group; Placebo Group

Hydroxychloroquine DRUG

Active Drug

Also known as: HCQ, Chloroquine

Hydroxychloroquine (HCQ) Group

Matching Placebo DRUG

Matching Placebo for the control group.

Also known as: Placebo

Placebo Group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Veteran
• Age 18-80 years;
• Moderate to severe CKD at the time of screening, defined as one of the following: 1) Stage 3b or 4 CKD with latest eGFR of 25-59, with diabetes mellitus, OR 2) Stage 3b or 4 CKD with latest eGFR of 25 to 45 mL/min and maximum recorded albuminuria defined as urine albumin/creatinine ratio (UACR) of 30 mg/g, OR 3) Stage 3a CKD with eGFR 46-59 ml/min with urine albumin/creatinine (UACR) 100 mg/gm

You may not qualify if:

• G6PD deficiency or known hypersensitivity to 4-aminoquinoline
• Conventional contraindications for non-contrast MRI examination including
• Permanent pacemaker
• Automatic Implantable Cardioverter Defibrillator
• Significant fear of closed space
• Claustrophobia that prevents patients from participating
• Inability to lie down
• Abnormal liver functions or diagnosis of cirrhosis
• AST and ALT more than 1.5 times the normal or INR without being anti-coagulated greater than 1.4
• History of documented non-adherence to therapy
• Inability to attend treatment or follow-up scheduling
• Less than 6 months since initiation of 'Statins'
• Prior history of any dialysis within last 12 months, or history of diagnosed AKI in the prior three months
• History of acute cardiovascular event defined as:
• myocardial infarction

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

North Florida/South Georgia Veterans Health System, Gainesville, FL

Gainesville, Florida, 32608-1135, United States

Location

Related Publications (2)

• Shukla AM, Segal MS, Pepine CJ, Cheung AK, Shuster J, Mohandas R, Martinez WM, Flint JJ, Shah SV. Management of Cardiovascular Disease in Kidney Disease Study: Rationale and Design. Am J Nephrol. 2021;52(1):36-44. doi: 10.1159/000513567. Epub 2021 Feb 26.

  PMID: 33640890 BACKGROUND

• Joyce M, Segal MS, Shukla AM. Ethics and Terminology for Opting In and Out. JAMA Intern Med. 2024 Apr 1;184(4):451-452. doi: 10.1001/jamainternmed.2023.7060. No abstract available.

  PMID: 38372980 BACKGROUND

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Cardiovascular Diseases; Inflammation; Atherosclerosis

Interventions

Vascular Stiffness; Hydroxychloroquine; Chloroquine

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Cardiovascular Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ashutosh M. Shukla, MD MBBS

  North Florida/South Georgia Veterans Health System, Gainesville, FL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Randomized Double Blind Placebo Controlled Study

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: August 17, 2018
• Study Start: December 14, 2018
• Primary Completion: January 31, 2024
• Study Completion: January 31, 2024
• Last Updated: February 10, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)