Ignite Creation Date:
2025-12-25 @ 4:46 AM
Ignite Modification Date:
2025-12-26 @ 3:48 AM
Study NCT ID:
NCT01132118
Status:
COMPLETED
Last Update Posted:
2014-09-03
First Post:
2010-05-25
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis
Sponsor:
Brigham and Women's Hospital
Organization:
Study Overview
Official Title:
Hydroxychloroquine to Improve Insulin Sensitivity in Rheumatoid Arthritis
Status:
COMPLETED
Status Verified Date:
2014-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
RA PLUS
Brief Summary:
The purpose of this study is to determine whether hydroxychloroquine (HCQ) reduces insulin resistance in non-diabetic subjects with rheumatoid arthritis (RA). The investigators will conduct a double-blind randomized crossover trial in subjects with RA to test the hypothesis that HCQ improves insulin sensitivity. The investigators will also use data from the trial to identify determinants of insulin resistance in RA. The investigators hypothesize that RA will be associated with an increased risk of insulin resistance and that independent risk factors for increased insulin resistance in RA include higher BMI, elevated acute phase reactants, greater fat to muscle ratio, and less physical activity.
Detailed Description:
Our ability to better control the pain and disability of rheumatoid arthritis (RA) now focuses attention on reducing the impact of RA-associated comorbidities. The most common cause of death in RA is cardiovascular (CV) disease, and the risk of myocardial infarction and stroke are approximately doubled in RA. The determinants of CV risk in RA include traditional CV risk factors as well as aspects of the inflammatory process defining RA. It is likely that RA-associated inflammation accelerates atherosclerosis through direct effects on the endothelium as well as indirect effects on insulin metabolism. Several studies report an increased prevalence of insulin resistance among persons with RA. However, it is not clear whether the inflammation of RA causes insulin resistance. Corticosteroids and abnormalities in the hypothalamic-pituitary axis may also contribute to abnormal glucose metabolism. Little information is available to guide management of a pre-diabetic insulin resistance state in RA.
Hydroxychloroquine (HCQ), a commonly used medicine early in RA, may play a role in improving insulin resistance. Several previous trials demonstrated the ability of HCQ to reduce blood glucose levels in diabetics, and a large epidemiologic study found that subjects with RA using HCQ were less likely to develop diabetes. In animal models, anti-malarials lower blood glucose through slowing insulin metabolism.
With CV disease a major comorbidity in RA and insulin resistance possibly a major determinant of CV risk, intervention studies need to begin to translate prior work into clinical therapeutics.
Relevance: If this study demonstrates a beneficial effect of HCQ on insulin resistance among the randomized subjects, this would provide strong evidence that HCQ has benefits beyond RA and SLE disease activity. Currently, HCQ is stopped in many patients as they "step-up" to more aggressive DMARD treatments, or HCQ may never be tried in some patients who present with RA carrying with poor prognosis. If HCQ improves insulin sensitivity, there may be rationale for continuing HCQ chronically in patients with RA. As well, a larger clinical endpoint study would be strongly considered.
Hydroxychloroquine (HCQ), a commonly used medicine early in RA, may play a role in improving insulin resistance. Several previous trials demonstrated the ability of HCQ to reduce blood glucose levels in diabetics, and a large epidemiologic study found that subjects with RA using HCQ were less likely to develop diabetes. In animal models, anti-malarials lower blood glucose through slowing insulin metabolism.
With CV disease a major comorbidity in RA and insulin resistance possibly a major determinant of CV risk, intervention studies need to begin to translate prior work into clinical therapeutics.
Relevance: If this study demonstrates a beneficial effect of HCQ on insulin resistance among the randomized subjects, this would provide strong evidence that HCQ has benefits beyond RA and SLE disease activity. Currently, HCQ is stopped in many patients as they "step-up" to more aggressive DMARD treatments, or HCQ may never be tried in some patients who present with RA carrying with poor prognosis. If HCQ improves insulin sensitivity, there may be rationale for continuing HCQ chronically in patients with RA. As well, a larger clinical endpoint study would be strongly considered.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| R21AR057924 | NIH | None | https://reporter.nih.gov/quic… | View |