Metabolic Effects of Hydroxychloroquine

NCT ID: NCT02026232

Last Updated: 2023-12-28

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2012-03-31

Study Completion Date

2022-12-15

Brief Summary

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The basic plan of the study is to randomize otherwise healthy subjects with type 2 diabetes to hydroxychloroquine, 200 mg twice daily or placebo.

Detailed Description

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Hydroxychloroquine is a medicine that has been used for a long time to treat patients with malaria, rheumatoid arthritis, lupus and other conditions. It is closely related to chloroquine but with a better side effect profile for long term use. In treating these conditions it was discovered to have some beneficial properties like lowering cholesterol and lowering sugar in the blood of those who have diabetes. The mechanisms underlying these effects are unknown. In animal studies, we have discovered that chloroquine appears to decrease glucose, lower blood pressure and decrease atherosclerosis (hardening of the arteries). This collection of problems commonly occurs in the metabolic syndrome and diabetes mellitus, which affects over 20% and 7% of adults in Western countries respectively. We have recently looked at the effects of chloroquine on the metabolic syndrome in humans which showed that small doses given for a short period of time would reduce insulin resistance in patients with the metabolic syndrome. Several population studies have shown similar effects with hydroxychloroquine. Since hydroxychloroquine is similar to chloroquine, we thus expect similar effects on blood glucose, blood pressure and blood cholesterol in type 2 diabetes. This offers a unique opportunity to develop a novel approach for lowering blood pressure, lipids (cholesterol and triglycerides), and glucose in people at risk for heart disease

Conditions

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Type 2 Diabetes Mellitus

Keywords

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Type 2 Diabetes Overweight

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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hydroxychloroquine

hydroxychloroquine twice daily for 4 weeks

Group Type ACTIVE_COMPARATOR

Hydroxychloroquine

Intervention Type DRUG

200mg twice daily

Placebo

hydroxychloroquine placebo twice daily for 4 weeks

Group Type PLACEBO_COMPARATOR

Hydroxychloroquine Placebo

Intervention Type OTHER

200mg placebo twice daily

Interventions

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Hydroxychloroquine

200mg twice daily

Intervention Type DRUG

Hydroxychloroquine Placebo

200mg placebo twice daily

Intervention Type OTHER

Other Intervention Names

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Plaquenil Quineprox placebo

Eligibility Criteria

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Inclusion Criteria

* Subjects between the age of 18 and 75, either gender, any ethnic group
* Subjects must have type 2 diabetes and the following:
* A1c of 6.5-9.0%
* Treated with at least 1000 mg of metformin daily with or without a dipeptidyl peptidase-4(DPP4)inhibitor, a sulfonylurea (glipizide, glyburide, glimepiride),bromocriptine or colesevelam.
* Subjects should have a BMI \>27

Exclusion Criteria

* Prior treatment with chloroquine or hydroxychloroquine as follows:

1. any exposure in the past 2 years,
2. \>30 days of therapy if exposure was between 2 and 5 years ago,
3. \>90 days of therapy if exposure was between 5 and 10 years ago,
4. \>6 months of therapy if exposure was 10 to 20 years ago,
5. \>1 year of therapy if exposure was 20 to 30 years ago,
6. No limit if last exposure was \>30 years ago, e.g. during the Vietnam conflict.
* Morbid obesity (BMI \>45)
* Coronary artery disease or other vascular disease
* History of stroke
* Serum creatinine \>-4 mg/dl for women and \>-5 mg/dl for men.
* Seizure disorder
* History of psoriasis
* Hematologic disorders, including anemia (WHO criteria for anemia:hemoglobin \<13g/dL in men and \<12 g/dL in women)
* Current malignancy or active treatment for recurrence prevention,e.g. tamoxifen. Cancer considered to be cured, either as a result of surgery or other treatment is not exclusionary.
* Asthma requiring daily beta agonist therapy or intermittent oral steroids is exclusionary. Inhaled steroids are acceptable. Obstructive sleep apnea will be allowed if continuous positive airway pressure(CPAP) or other therapy has been stable for 6 months. Other active respiratory diseases are excluded.
* Treatment with 50mg or greater of Metoprolol or treatment with digoxin
* Liver disease, or Liver Function Test \>2 times normal
* Active infection (including HIV)
* Serious illness requiring ongoing medical care or medication
* Treatment with atypical anti-psychotic medication. Treatment with any other medication for psychiatric illness, unless on a stable dose for 6 weeks prior to enrollment. Patients with unstable psychiatric disorders are excluded per the decision of the study MD regardless of medication history.
* Taking any of the following lipid lowering medications: niacin, fibrates, and greater than 1 gm/day of fish oils
* Uncontrolled hypertension (BP \>150/90 mm Hg) at enrollment
* Need for daily Over The Counter medications, or currently taking cimetidine or \>1000 IU vitamin E daily and unwilling to reduce or discontinue vitamin E or discontinue cimetidine for the duration of the study. Patients taking more than 1000 IU vitamin E daily should reduce or discontinue the vitamin for 30 days before randomization.
* Pregnant or lactating women, or women intending to become pregnant
* Women not using adequate birth control (hormonal birth control is acceptable, also double barrier)
* QT corrected \>450 msec on screening ECG
* Glucose-6-phosphate dehydrogenase (G6PD) deficiency
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clay F. Semenkovich, M.D.

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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Rao Kondapally Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njolstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J; Emerging Risk Factors Collaboration. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011 Mar 3;364(9):829-841. doi: 10.1056/NEJMoa1008862.

Reference Type BACKGROUND
PMID: 21366474 (View on PubMed)

Schramm TK, Gislason GH, Kober L, Rasmussen S, Rasmussen JN, Abildstrom SZ, Hansen ML, Folke F, Buch P, Madsen M, Vaag A, Torp-Pedersen C. Diabetes patients requiring glucose-lowering therapy and nondiabetics with a prior myocardial infarction carry the same cardiovascular risk: a population study of 3.3 million people. Circulation. 2008 Apr 15;117(15):1945-54. doi: 10.1161/CIRCULATIONAHA.107.720847. Epub 2008 Mar 31.

Reference Type BACKGROUND
PMID: 18378618 (View on PubMed)

Schneider JG, Finck BN, Ren J, Standley KN, Takagi M, Maclean KH, Bernal-Mizrachi C, Muslin AJ, Kastan MB, Semenkovich CF. ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome. Cell Metab. 2006 Nov;4(5):377-89. doi: 10.1016/j.cmet.2006.10.002.

Reference Type BACKGROUND
PMID: 17084711 (View on PubMed)

Marmor MF, Kellner U, Lai TY, Lyons JS, Mieler WF; American Academy of Ophthalmology. Revised recommendations on screening for chloroquine and hydroxychloroquine retinopathy. Ophthalmology. 2011 Feb;118(2):415-22. doi: 10.1016/j.ophtha.2010.11.017.

Reference Type BACKGROUND
PMID: 21292109 (View on PubMed)

Su Y, Swift M. Mortality rates among carriers of ataxia-telangiectasia mutant alleles. Ann Intern Med. 2000 Nov 21;133(10):770-8. doi: 10.7326/0003-4819-133-10-200011210-00009.

Reference Type BACKGROUND
PMID: 11085839 (View on PubMed)

Razani B, Feng C, Semenkovich CF. p53 is required for chloroquine-induced atheroprotection but not insulin sensitization. J Lipid Res. 2010 Jul;51(7):1738-46. doi: 10.1194/jlr.M003681. Epub 2010 Mar 5.

Reference Type BACKGROUND
PMID: 20208057 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://rpr.wustl.edu/

Washington University Research Patient Registry

Other Identifiers

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201110258

Identifier Type: OTHER

Identifier Source: secondary_id

201110258

Identifier Type: -

Identifier Source: org_study_id