Chronic Kidney DiseasePhase 2MaCKNCT03636152
Management of Cardiovascular Disease in Kidney Disease (MaCK) Study
A Phase 2 study testing MRI carotid, APWV and Hydroxychloroquine in people with Chronic Kidney Disease and Cardiovascular Disease, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Kidney Disease, Cardiovascular Disease, Inflammation
- What is being tested?
- MRI carotid, APWV and Hydroxychloroquine
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Dec 2018to 31 Jan 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 27Show fewer
- 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
- stroke or new diagnosis of congestive heart failure or heart failure related admission in prior 3 months
- History of prolonged QTc interval 450, For patients with BBB an adjusted QT interval >450
- Known chronic active infections like HIV, Hepatitis B or Hepatitis C positive, chronic osteomyelitis etc.
- Recent serious infection including requiring hospitalization within 3 months or Recent minor infection such as skin, soft tissue or respiratory infections within 30 days of enrollment
- Active or recently treated (< 1 year in remission) malignancy, transplantation, or systemic inflammatory diseases
- Patients with localized squamous cell carcinoma of the skin are eligible
- Use of systemic corticosteroids or other immunosuppression within last 3 months (acute course of steroid for a gouty arthritis or chronic obstructive pulmonary disease is eligible if > 1 month ago)
- Pregnancy, breastfeeding or planning to become pregnant during the course of the study
- Life expectancy less than 12 months or uncontrolled congestive heart failure (CHF)
- defined as more than 2 admissions in prior 6 months)
- Any other condition the PI determines may put the research subject in jeopardy during the course of the study
- Recent unexplained weight loss or vision changes
Trial locations and contacts
1 site in 1 country.
United States1 site
North Florida/South Georgia Veterans Health System, Gainesville, FL
Gainesville, Florida, 32608-1135
About this study
Official title: Hydroxychloroquine for the Management of CVD in CKD
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.
Read the detailed description
Cardiovascular disease (CVD) is the most prominent cause of morbidity and mortality among patients with chronic kidney disease (CKD), and end stage kidney disease (ESKD). Unfortunately at the present time, the investigators do not have an effective treatment to reduce the high CVD mortality in these populations. Accelerated atherosclerosis, inflammation, and vascular stiffness are prominent factors contributing to CVD in CKD. Interventions that can effectively counter these factors may provide significant benefits for the management of CVD in CKD. Hydroxychloroquine (HCQ) is an inexpensive and safe anti-inflammatory drug that has been in clinical use for over 4 decades even in patients with CKD and ESKD. In recent times, multiple in vitro, in vivo, and human cohort based data have shown that HCQ benefits multiple parameters of CVD, including inflammation, endothelial function, metabolic syndrome, insulin sensitivity and atherosclerosis. Recently the investigators through the animal studies validated that HCQ indeed has significant anti-atherosclerosis and vasculoprotective effects in CKD milieu. The investigators further conducted a small, human, feasibility study that shows a potential for HCQ on parameters relevant to CVD in CKD. As the next step, the investigators propose to conduct a proof-of-concept, randomized controlled trial (RCT) to ascertain the effects of HCQ on the structural, functional, and biochemical measures of atherosclerosis and CVD. The investigators will enroll 100 albuminuric, stage 3b CKD subjects in a with 1:1 allocation (HCQ : placebo) and treat for a duration of 18 months. The investigators' three specific aims are as follows: Specific Aim (SA) 1 will evaluate the ability of HCQ, compared to placebo, to slow the progression, or reverse atherosclerosis through serial examination of carotid atherosclerosis through non-contrast MRI performed at baseline and after 9 and 18 months of treatment with HCQ or placebo. The investigators will measure the change in total carotid plaque volume (TPV) as the primary outcome measure, and changes in total plaque surface area, maximal stenosis, and the type (fibrous, stable, or unstable), and stability of plaques as secondary outcome measures. SA2 will evaluate the impact of HCQ vs. placebo on inflammation (SA2a), and vascular stiffness (SA2b) at baseline, and at 6, 9, 12, and 18 months as secondary outcome measures. The investigators will quantify inflammation through high-sensitivity C-reactive protein (SA2a) and vascular stiffness through measurements of aortic pulse wave velocity (SA2b). Specific Aim 3 will examine the effect of HCQ and placebo on the trends of hard cardiac and renal outcomes and drug safety. The results of this trial will provide critical preliminary data to justify and plan a definitive, multicenter RCT to examine the effects of HCQ on hard outcomes of CVD in CKD. Additionally, this study may provide insights into the importance of select inflammatory and vascular factors in CVD with wider future implications for those with CKD and perhaps the general population.
- Conditions
- Chronic Kidney Disease, Cardiovascular Disease, Inflammation, Atherosclerosis, Aortic Stiffness
- Being tested
- MRI carotid, APWV, Hydroxychloroquine, Matching Placebo
- Keywords
- chronic kidney disease, cardiovascular disease, Inflammation, Atherosclerosis, Vascular stiffness
- Medical subject headings
- Renal Insufficiency, Chronic, Cardiovascular Diseases, Inflammation, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRI carotidProcedure or surgery
Also called Carotid MRI
To assess the carotid atherosclerotic plaques
APWVProcedure or surgery
Also called aortic pulse wave velocity, pulse wave velocity, vascular stiffness
Doppler measurement of the APWV
Also called HCQ, Chloroquine
Active Drug
Matching PlaceboDrug
Also called Placebo
Matching Placebo for the control group.
| Study group | Role | What they receive |
|---|---|---|
| Hydroxychloroquine (HCQ) Group | Active comparator | These patients will receive HCQ for 18 months Receives: Procedure: MRI carotid; Procedure: APWV; Drug: Hydroxychloroquine |
| Placebo Group | Placebo comparator | These patients will receive a matching placebo for 18 months Receives: Procedure: MRI carotid; Procedure: APWV; Drug: Matching Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total Plaque Volume (TPV), Carotid
Measurements of Carotid TPV at enrollment and serially over 18th months
Measured: Baseline, 9 months, 18 months
Secondary outcomes (2)
High Sensitivity C-Reactive Protein (hsCRP)
Measurements of hsCRP at enrollment and serially over 18 months
Measured: Baseline, 9 months, 18 months
Aortic Pulse Wave Velocity (APWV)
Measurements of APWV at enrollment and serially over 18 months
Measured: Baseline, 9 months, 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2018
- Study start14 Dec 2018
- Primary completion31 Jan 2024
- Study completion31 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized Double Blind Placebo Controlled Study
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Ashutosh M. Shukla, MD MBBS, Principal investigator, North Florida/South Georgia Veterans Health System, Gainesville, FL
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03636152
- Sponsor's protocol ID
- CARB-013-17F
- Other IDs
- ICX001661A
- Acronym
- MaCK
- Status last verified
- Aug 2026
- First submitted
- 10 Aug 2018
- Last updated
- 20 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33640890Joyce 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.
PubMed 38372980
Study at a glance
From the registry record, last updated by the sponsor on 20 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxychloroquine for the Management of CVD in CKD
- ClinicalTrials.gov ID
- NCT03636152
- Acronym / sponsor ID
- MaCK / CARB-013-17F
- Conditions
- Chronic Kidney Disease, Cardiovascular Disease, Inflammation, Atherosclerosis, Aortic Stiffness
- Keywords
- chronic kidney disease, cardiovascular disease, Inflammation, Atherosclerosis, Vascular stiffness
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 14 Dec 2018 (actual)
- Primary completion
- 31 Jan 2024 (actual)
- Study completion
- 31 Jan 2024 (actual)
- First posted
- 17 Aug 2018 (actual)
- Results
- Posted 20 Aug 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Cardiovascular disease (CVD) is the most prominent cause of morbidity and mortality among patients with chronic kidney disease (CKD), and end stage kidney disease (ESKD). Unfortunately at the present time, the investigators do not have an effective treatment to reduce the high CVD mortality in these populations. Accelerated atherosclerosis, inflammation, and vascular stiffness are prominent factors contributing to CVD in CKD. Interventions that can effectively counter these factors may provide significant benefits for the management of CVD in CKD. Hydroxychloroquine (HCQ) is an inexpensive and safe anti-inflammatory drug that has been in clinical use for over 4 decades even in patients with CKD and ESKD. In recent times, multiple in vitro, in vivo, and human cohort based data have shown that HCQ benefits multiple parameters of CVD, including inflammation, endothelial function, metabolic syndrome, insulin sensitivity and atherosclerosis. Recently the investigators through the animal studies validated that HCQ indeed has significant anti-atherosclerosis and vasculoprotective effects in CKD milieu. The investigators further conducted a small, human, feasibility study that shows a potential for HCQ on parameters relevant to CVD in CKD. As the next step, the investigators propose to conduct a proof-of-concept, randomized controlled trial (RCT) to ascertain the effects of HCQ on the structural, functional, and biochemical measures of atherosclerosis and CVD. The investigators will enroll 100 albuminuric, stage 3b CKD subjects in a with 1:1 allocation (HCQ : placebo) and treat for a duration of 18 months. The investigators' three specific aims are as follows: Specific Aim (SA) 1 will evaluate the ability of HCQ, compared to placebo, to slow the progression, or reverse atherosclerosis through serial examination of carotid atherosclerosis through non-contrast MRI performed at baseline and after 9 and 18 months of treatment with HCQ or placebo. The investigators will measure the change in total carotid plaque volume (TPV) as the primary outcome measure, and changes in total plaque surface area, maximal stenosis, and the type (fibrous, stable, or unstable), and stability of plaques as secondary outcome measures. SA2 will evaluate the impact of HCQ vs. placebo on inflammation (SA2a), and vascular stiffness (SA2b) at baseline, and at 6, 9, 12, and 18 months as secondary outcome measures. The investigators will quantify inflammation through high-sensitivity C-reactive protein (SA2a) and vascular stiffness through measurements of aortic pulse wave velocity (SA2b). Specific Aim 3 will examine the effect of HCQ and placebo on the trends of hard cardiac and renal outcomes and drug safety. The results of this trial will provide critical preliminary data to justify and plan a definitive, multicenter RCT to examine the effects of HCQ on hard outcomes of CVD in CKD. Additionally, this study may provide insights into the importance of select inflammatory and vascular factors in CVD with wider future implications for those with CKD and perhaps the general population.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized Double Blind Placebo Controlled Study
| Arm | Type | Receives |
|---|---|---|
| Hydroxychloroquine (HCQ) Group | Active comparator | Procedure: MRI carotid, Procedure: APWV, Drug: HydroxychloroquineThese patients will receive HCQ for 18 months |
| Placebo Group | Placebo comparator | Procedure: MRI carotid, Procedure: APWV, Drug: Matching PlaceboThese patients will receive a matching placebo for 18 months |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (27 listed)
- G6PD deficiency or known hypersensitivity to 4-aminoquinoline
- Conventional contraindications for non-contrast MRI examination including
- Abnormal liver functions or diagnosis of cirrhosis
- History of documented non-adherence to therapy
- Less than 6 months since initiation of 'Statins'
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRI carotidAlso: Carotid MRITo assess the carotid atherosclerotic plaques | Procedure or surgery | Hydroxychloroquine (HCQ) Group, Placebo Group |
| APWVAlso: aortic pulse wave velocity, pulse wave velocity, vascular stiffnessDoppler measurement of the APWV | Procedure or surgery | Hydroxychloroquine (HCQ) Group, Placebo Group |
| HydroxychloroquineAlso: HCQ, ChloroquineActive Drug | Drug | Hydroxychloroquine (HCQ) Group |
| Matching PlaceboAlso: PlaceboMatching Placebo for the control group. | Drug | Placebo Group |
Primary outcome
Total Plaque Volume (TPV), Carotid
Time frame: Baseline, 9 months, 18 months
Measurements of Carotid TPV at enrollment and serially over 18th months
2 secondary outcomes
High Sensitivity C-Reactive Protein (hsCRP)
Time frame: Baseline, 9 months, 18 months
Aortic Pulse Wave Velocity (APWV)
Time frame: Baseline, 9 months, 18 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Aug 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 33640890Shukla 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.
- Background: PubMed 38372980Joyce 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashutosh M. Shukla, MD MBBS principal investigator
North Florida/South Georgia Veterans Health System, Gainesville, FL
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MRI carotid, APWV and Hydroxychloroquine in people with Chronic Kidney Disease and Cardiovascular Disease, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Total Plaque Volume (TPV), Carotid (time frame: Baseline, 9 months, 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03636152, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2026.