Kidney Failure, ChronicPhase 2NCT01537315
Hydroxychloroquine in Cardiovascular Disease in Patients With Chronic Kidney Disease: A Proof of Concept Study
A Phase 2 study testing Hydroxychloroquine in people with Kidney Failure, Chronic and Cardiovascular Disease, run by University of Arkansas at 3 sites in United States.
Trial summary
Presence of multiple traditional and nontraditional risk factors of atherosclerosis and cardiovascular disease (CVD) including inflammation in patients with chronic kidney disease (CKD) contribute to high CVD morbidity and mortality in this patient population. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Kidney Failure, Chronic, Cardiovascular Disease, Arteriosclerosis
- What is being tested?
- Hydroxychloroquine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 3 sitesUnited States
- Study dates
- Feb 2012to Sep 2013
- 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
- Measured stage IV proteinuric chronic kidney disease with an estimated Modification of Diet in Renal Disease (MDRD) GFR (eGFR) of 18 to 35 ml/min.
- Current or history of documented proteinuria of more than or equal to 300 mg/dL in 24 hours or a spot urine protein to creatinine ratio of greater than 0.3 ug/mg.
- Not on dialysis.
- Ages 18 to 80 years, both sexes, all races and ethnicities
Who cannot join
- glucose-6-phosphate dehydrogenase (G6PD) deficiency or known hypersensitivity to 4-aminoquinoline compounds (such as chloroquine or hydroxychloroquine).
- Abnormal liver functions; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) more than 2.5 times the normal or international normalized ratio (INR) without being anti-coagulated greater than 1.4.
- Known chronic active infections like HIV, Hepatitis B or Hepatitis C positive, chronic osteomyelitis etc.
- Recent serious infection including Pneumonia requiring hospitalization, meningitis, septicemia in the 2 months prior to screening.
- Active or recently treated (< 1 year in remission) malignancy or systemic inflammatory diseases (Patients with localized squamous cell carcinoma of the skin are eligible).
- Pregnancy, breastfeeding or planning to become pregnant during the course of the study.
Show all 11Show fewer
- Use of systemic corticosteroids or other immunosuppression within last 3 months (acute course of steroid for a gouty arthritis or chronic obstructive pulmonary disease (COPD) is eligible if > 1 month ago).
- History of prolonged corrected QT interval > 450.
- Inability to attend or comply with treatment or follow-up scheduling.
- Life expectancy less than 6 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Florida
Gainesville, Florida, 32610-0224
Central Arkansas Veterans Healthcare System
Little Rock, Arkansas, 72205
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
About this study
Presence of multiple traditional and nontraditional risk factors of atherosclerosis and cardiovascular disease (CVD) including inflammation in patients with chronic kidney disease (CKD) contribute to high CVD morbidity and mortality in this patient population. Additionally, the traditional approaches towards the therapy of CVD have little impact on CV mortality in these patients. Hydroxychloroquine (HCQ) used as anti-inflammatory in rheumatological disorders, has multiple beneficial properties relevant to the process of vascular disease. The effects of HCQ on atherosclerosis (AS) and vascular disease in CKD is not known yet. Thus, the study hypothesis is that HCQ treatment in individuals with CKD will provide clinically significant benefit in the management of CVD and will provide biological and functional atherosclerotic benefits.
Read the detailed description
This pilot study has been designed to look at the impact of hydroxychloroquine (HCQ) in the clinical model of accelerated atherosclerosis (AS) in the chronic kidney disease (CKD) population. This intervention is designed to have an impact on the initiation and progression of AS by reducing systemic inflammation, improving or restoring vascular endothelial function, and by improving the milieu of metabolic syndrome and insulin resistance.
The current study is a proof of concept study for the expansion of the use of HCQ for a new indication for the treatment of AS and cardiovascular disease (CVD) in patients with CKD.University of Arkansas for Medical Sciences (UAMS) has filed an Investigational New Drug (IND) for a new indication on 4/28/11. The FDA responded that this study is exempt from an IND.
This "Proof-of-Concept" randomized double blinded placebo controlled study will evaluate the nature and extent of HCQ effects, and if found significantly beneficial, it will be used to guide the development of a large, multicenter, randomized control trial of HCQ to examine the hard clinical end points of CVD and mortality in patients with advanced CKD. The investigators propose to enroll 62 subjects to achieve the effects of HCQ in 52 individuals (39 HCQ group and 13 placebo group).
- Being tested
- Hydroxychloroquine, Matching Placebo
- Keywords
- Kidney Failure, Chronic, Cardiovascular Disease, Arteriosclerosis
- Medical subject headings
- Kidney Failure, Chronic, Cardiovascular Diseases, Arteriosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Also called Plaquenil
200 mg capsule daily for 10 +/- 4 days, then 200 mg twice daily till end of study (duration approximately 6 months)
Matching PlaceboOther
matching placebo capsule 200 mg daily for 10 +/- 4 days and thereafter 200 mg twice a day for duration of study, approximately 6 months
| Study group | Role | What they receive |
|---|---|---|
| Matching Placebo | Placebo comparator | Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) will be randomized to either hydroxychloroquine (HCQ) or matching placebo in a 3:1 ratio (approximately 39 to HCQ and 13 to placebo) Receives: Other: Matching Placebo |
| Hydroxychloroquine | Experimental | Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) will be randomized to either hydroxychloroquine (HCQ) or matching placebo in a 3:1 ratio (approximately 39 to HCQ and 13 to placebo) Receives: Drug: Hydroxychloroquine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Inflammatory Marker, Hs-C Reactive Protein, at 6 Months
Hs-CRP will be measured at baseline (before study drug) and at end of study (6 months). This marker is measured by ELISA assay from serum.
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2012 (estimated)
- Study startFeb 2012
- Primary completionSep 2013
- Study completionSep 2013
Why it stopped: lack of funding
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.
- Other trials for Kidney Failure, ChronicStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe 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
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dumitru Rotaru, MD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01537315
- Sponsor's protocol ID
- 132036
- Status last verified
- Nov 2014
- First submitted
- 10 Feb 2012
- Last updated
- 19 Nov 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hydroxychloroquine in Cardiovascular Disease in Patients With Chronic Kidney Disease: A Proof of Concept Study
- ClinicalTrials.gov ID
- NCT01537315
- Acronym / sponsor ID
- 132036
- Keywords
- Kidney Failure, Chronic, Cardiovascular Disease, Arteriosclerosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of funding
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Study start
- Feb 2012
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 23 Feb 2012 (estimated)
- Results
- Posted 19 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Presence of multiple traditional and nontraditional risk factors of atherosclerosis and cardiovascular disease (CVD) including inflammation in patients with chronic kidney disease (CKD) contribute to high CVD morbidity and mortality in this patient population. Additionally, the traditional approaches towards the therapy of CVD have little impact on CV mortality in these patients. Hydroxychloroquine (HCQ) used as anti-inflammatory in rheumatological disorders, has multiple beneficial properties relevant to the process of vascular disease. The effects of HCQ on atherosclerosis (AS) and vascular disease in CKD is not known yet. Thus, the study hypothesis is that HCQ treatment in individuals with CKD will provide clinically significant benefit in the management of CVD and will provide biological and functional atherosclerotic benefits.
Detailed description
This pilot study has been designed to look at the impact of hydroxychloroquine (HCQ) in the clinical model of accelerated atherosclerosis (AS) in the chronic kidney disease (CKD) population. This intervention is designed to have an impact on the initiation and progression of AS by reducing systemic inflammation, improving or restoring vascular endothelial function, and by improving the milieu of metabolic syndrome and insulin resistance.
The current study is a proof of concept study for the expansion of the use of HCQ for a new indication for the treatment of AS and cardiovascular disease (CVD) in patients with CKD.University of Arkansas for Medical Sciences (UAMS) has filed an Investigational New Drug (IND) for a new indication on 4/28/11. The FDA responded that this study is exempt from an IND.
This "Proof-of-Concept" randomized double blinded placebo controlled study will evaluate the nature and extent of HCQ effects, and if found significantly beneficial, it will be used to guide the development of a large, multicenter, randomized control trial of HCQ to examine the hard clinical end points of CVD and mortality in patients with advanced CKD. The investigators propose to enroll 62 subjects to achieve the effects of HCQ in 52 individuals (39 HCQ group and 13 placebo group).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Matching Placebo | Placebo comparator | Other: Matching PlaceboPatients with cardiovascular disease (CVD) and chronic kidney disease (CKD) will be randomized to either hydroxychloroquine (HCQ) or matching placebo in a 3:1 ratio (approximately 39 to HCQ and 13 to placebo) |
| Hydroxychloroquine | Experimental | Drug: HydroxychloroquinePatients with cardiovascular disease (CVD) and chronic kidney disease (CKD) will be randomized to either hydroxychloroquine (HCQ) or matching placebo in a 3:1 ratio (approximately 39 to HCQ and 13 to placebo) |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Measured stage IV proteinuric chronic kidney disease with an estimated Modification of Diet in Renal Disease (MDRD) GFR (eGFR) of 18 to 35 ml/min.
- Current or history of documented proteinuria of more than or equal to 300 mg/dL in 24 hours or a spot urine protein to creatinine ratio of greater than 0.3 ug/mg.
- Not on dialysis.
- Ages 18 to 80 years, both sexes, all races and ethnicities
Key exclusion criteria (11 listed)
- glucose-6-phosphate dehydrogenase (G6PD) deficiency or known hypersensitivity to 4-aminoquinoline compounds (such as chloroquine or hydroxychloroquine).
- Abnormal liver functions; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) more than 2.5 times the normal or international normalized ratio (INR) without being anti-coagulated greater than 1.4.
- Known chronic active infections like HIV, Hepatitis B or Hepatitis C positive, chronic osteomyelitis etc.
- Recent serious infection including Pneumonia requiring hospitalization, meningitis, septicemia in the 2 months prior to screening.
- Active or recently treated (< 1 year in remission) malignancy or systemic inflammatory diseases (Patients with localized squamous cell carcinoma of the skin are eligible).
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 |
|---|---|---|
| HydroxychloroquineAlso: Plaquenil200 mg capsule daily for 10 +/- 4 days, then 200 mg twice daily till end of study (duration approximately 6 months) | Drug | Hydroxychloroquine |
| Matching Placebomatching placebo capsule 200 mg daily for 10 +/- 4 days and thereafter 200 mg twice a day for duration of study, approximately 6 months | Other | Matching Placebo |
Primary outcome
Change From Baseline in Inflammatory Marker, Hs-C Reactive Protein, at 6 Months
Time frame: Baseline and 6 months
Hs-CRP will be measured at baseline (before study drug) and at end of study (6 months). This marker is measured by ELISA assay from serum.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Dumitru Rotaru, MD principal investigator
University of Arkansas
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxychloroquine in people with Kidney Failure, Chronic and Cardiovascular Disease, run by University of Arkansas at 3 sites 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 4 inclusion and 11 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: stopped early, as of the sponsor's last update on 19 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 19 Nov 2014). 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?
Change From Baseline in Inflammatory Marker, Hs-C Reactive Protein, at 6 Months (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Nov 2014.