Atheroma Reduction With Chloroquine in Patients With the Metabolic Syndrome (ARCH-MS)

NCT00455403 | Completed Results DMC

• 2 other identifiers: 201110238(3)P50HL083762
• Study Type: interventional
• Target: 357
• Locations: 1 country
• Sites: 1

Brief Summary

Metabolic syndrome consists of a group of co-occuring conditions that increase an individual's risk of developing heart disease, stroke, and diabetes. The purpose of this study is to evaluate the long-term effectiveness of chloroquine, a protein-activation medication, at reducing the progression of atherosclerosis in patients with the metabolic syndrome. Sub-study: Vascular endothelial growth factor(VEGF)and Cardiometabolic Risk, The purpose is to determine if the association of VEGF with atherosclerosis indicates that it should be a marker of the disorder.

Conditions

Metabolic Syndrome X; Overweight; Hypertension; Dyslipidemias; Prediabetic State

Keywords

Metabolic Syndrome; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Change in Carotid Intima-media Thickness From Baseline to Year 1

  A noninvasive predictor of cardiovascular events, Carotid artery intima-media thickness (CIMT) was measured from B-mode images by a single sonographer using standard approaches

  Measured at baseline and year 1

Study Arms (2)

Chloroquine Subjects

EXPERIMENTAL

Participants will receive 80 mg of chloroquine on a daily basis.

Drug: Chloroquine

Placebo Subjects

PLACEBO COMPARATOR

Participants will receive a placebo comparator tablet on a daily basis.

Drug: Placebo Comparator

Interventions

Chloroquine DRUG

One tablet of 80 mg of chloroquine on a daily basis for 12 months followed by 12 months off drug with 1 visit at month 24

Also known as: Arlen

Chloroquine Subjects

Placebo Comparator DRUG

Chloroquine Placebo tablet daily for 12 months followed by 12 months off drug with 1 visit at month 24

Also known as: placebo

Placebo Subjects

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of metabolic syndrome, as determined by at least three of the following five criteria:
• Elevated fasting triglyceride level greater than 150 mg/dL
• Low HDL cholesterol levels: less than 50 mg/dL for women and less than 40 mg/dL for men
• Hypertension (greater than or equal to 130/85 mm Hg and less than or equal to 160/100 mm Hg) untreated; or hypertension controlled (less than or equal to 150/90 mm Hg) on a stable medication regimen for 4 weeks prior to baseline visit.
• Increased waist circumference: greater than 35 inches in women and greater than 40 inches in men
• Elevated fasting glucose level greater than or equal to 100 mg/dL and less than or equal to 126 mg/dL
• Willing to use acceptable form of birth control
• Subjects may be on a stable doses of a statin drug for at least 3 months
• Subjects may be on a stable doses of L-thyroxine for at least 3 months

You may not qualify if:

• Prior travel treatment with chloroquine or hydroxychloroquine as follows:
• Any exposure in the past 2 years
• More than 30 days of therapy if exposure was between 2 and 5 years ago
• More than 90 days of therapy if exposure was between 5 and 10 years ago
• More than 6 months of therapy if exposure was 10 to 20 years ago
• More than 1 year of therapy if exposure was 20 to 30 years ago
• No limit if last exposure was more than 30 years ago (e.g., during the Vietnam conflict)
• Morbid obesity (body mass index \[BMI\] greater than 45)
• Coronary artery disease or other vascular disease
• History of stroke
• Significant kidney disease (estimated glomerular filtration rate (eGFR)less than 60 mL/min/1.73 m2)
• Diabetes
• Seizure disorder
• History of psoriasis
• Blood disorders, including anemia (i.e., hemoglobin levels less than 13 g/dL in men and less than 12 g/dL in women)

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Singulex: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (2)

• McGill JB, Johnson M, Hurst S, Cade WT, Yarasheski KE, Ostlund RE, Schechtman KB, Razani B, Kastan MB, McClain DA, de las Fuentes L, Davila-Roman VG, Ory DS, Wickline SA, Semenkovich CF. Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness. Diabetol Metab Syndr. 2019 Jul 29;11:61. doi: 10.1186/s13098-019-0456-4. eCollection 2019.

  PMID: 31384309 DERIVED

• 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.

  PMID: 20208057 DERIVED

Related Links

• click here for Washington University Research Participant Registry

MeSH Terms

Conditions

Metabolic Syndrome; Overweight; Hypertension; Dyslipidemias; Prediabetic State; Atherosclerosis

Interventions

Chloroquine

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Lipid Metabolism Disorders; Diabetes Mellitus; Endocrine System Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

One limitation of the study is that it may have been underpowered to detect a difference in CIMT. Sample size estimates at the time of initiation of these studies were based on reports showing that insulin sensitizers had effects on CIMT with groups of 31-57 subjects, but subsequent work indicated the need for larger sample sizes.

Results Point of Contact

• Title: Janet McGill, MD
• Organization: Wash. Univ. School of Medicine

jmcgill@wustl.edu

314-362-8681

Study Officials

• Clay F. Semenkovich, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2007
• First Posted: April 3, 2007
• Study Start: April 1, 2006
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: December 15, 2021
• Results First Posted: June 25, 2021

Record last verified: 2021-12

Locations

US (1)