Chloroquine to Treat People With Metabolic Syndrome Aim2 (ARCH-MS)

NCT00455325 | Completed Phase 2 Results DMC

• 2 other identifiers: 395P50HL083762
• Study Type: interventional
• Target: 35
• 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 short-term effectiveness of chloroquine, a protein-activation medication, at improving metabolic syndrome.

Conditions

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

Keywords

Insulin Resistance; Atherosclerosis; Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• Insulin Sensitivity

  Hepatic insulin sensitivity was measured by comparing glucose production at baseline of zero insulin infusion rate with glucose production at 56 pmol/m2/min. Hepatic insulin sensitivity was expressed as the percent suppression, such that greater percent suppression indicated greater hepatic insulin sensitivity. There are no reference values, since the patients served as their own controls.

  assessed every 8 - 10 weeks at the end of each treatment period

Secondary Outcomes (6)

• Systolic Blood Pressure

  Assessed every 8-10 weeks at the end of each treatment period

• Diastolic Blood Pressure

  Assessed every 8-10 weeks at the end of each treatment period.

• Total Cholesterol

  Assessed every 8-10 weeks at the end of each treatment period.

• Non-HDL Cholesterol

  Assessed every 8-10 weeks at the end of each treatment period.

• Low-density Lipoprotein

  Assessed every 8-10 weeks at the end of each treatment period.

Study Arms (4)

First Intervention (3 weeks)

PLACEBO COMPARATOR

Cohort 1: Chloroquine placebo one tablet daily for 3 weeks, followed by 5-7 week rest period.

Drug: Placebo Comparator: First Intervention (3 weeks)

Second Intervention (3 weeks)

ACTIVE COMPARATOR

Cohort 2: 80mg chloroquine or placebo tablet once daily for Weeks 3, followed by 5-7 week rest period.

Drug: Active Comparator: Second Intervention (3 weeks)

Third Intervention (3 weeks)

ACTIVE COMPARATOR

Cohort 3: 80mg chloroquine tablet daily: for 3 weeks, followed by 5-7 week rest period.

Drug: Active Comparator: Third Intervention (3 weeks)

Fourth Intervention (3 weeks)

ACTIVE COMPARATOR

Cohort 4: 250mg chloroquine tablet daily: for 3 weeks, followed by 5-7 week rest period.

Drug: Active Comparator: Fourth Intervention (3 weeks)

Interventions

Placebo Comparator: First Intervention (3 weeks) DRUG

once daily placebo tablet for 3 weeks followed by: euglycemic clamp procedure; 24 hour Ambulatory Blood Pressure; Oral Glucose tolerance Test; serum collection; 24 hour urine collection; collection of peripheral blood mononuclear cells

Also known as: Placebo once daily

First Intervention (3 weeks)

Active Comparator: Second Intervention (3 weeks) DRUG

Once daily 80mg chloroquine or placebo tablet 3 Weeks followed by euglycemic clamp procedure; 24 hour Ambulatory Blood Pressure; Oral Glucose tolerance Test; serum collection; 24 hour urine collection; collection of peripheral blood mononuclear cells

Also known as: 80 mg chloroquine or placebo tablet once daily

Second Intervention (3 weeks)

Active Comparator: Third Intervention (3 weeks) DRUG

Once daily 80mg tablet for 3 weeks followed by: euglycemic clamp procedure; 24 hour Ambulatory Blood Pressure; Oral Glucose tolerance Test; serum collection; 24 hour urine collection; collection of peripheral blood mononuclear cells

Also known as: 80 mg chloroquine tablet once daily

Third Intervention (3 weeks)

Active Comparator: Fourth Intervention (3 weeks) DRUG

Once daily 250mg tablet for 3 weeks followed by: euglycemic clamp procedure; 24 hour Ambulatory Blood Pressure; Oral Glucose tolerance Test; serum collection; 24 hour urine collection; collection of peripheral blood mononuclear cells

Also known as: 250 mg chloroquine tablet once daily

Fourth Intervention (3 weeks)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of metabolic syndrome, as determined by at least three of the following five criteria:
• Elevated fasting triglyceride levels greater than or equal to 150 mg/dL
• Low HDL cholesterol levels: less than 50 mg/dL for women and less than 40 mg/dL for men
• Hypertension (=\>130/85 mm Hg =\<160/100 mm Hg) untreated; or hypertension controlled (=\<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 levels =\<100 mg/dL but =\>126 mg/dL
• 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
• Willing to use acceptable form of birth control (e.g., hormonal birth control, double barrier methods)

You may not qualify if:

• Prior travel treatment with chloroquine or hydroxychloroquine as follows:
• any exposure in the past 2 years,
• \>30 days of therapy if exposure was between 2 and 5 years ago,
• \>90 days of therapy if exposure was between 5 and 10 years ago,
• \>6 months of therapy if exposure was 10 to 20 years ago,
• \>1 year of therapy if exposure was 20 to 30 years ago,
• No limit if last exposure was \>30 years ago, ex. during the Vietnam conflict.
• Morbid obesity (body mass index \[BMI\] greater than 45)
• Coronary artery disease or other vascular disease
• History of stroke
• Chronic kidney insufficiency (i.e.,estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73m2)
• 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

Study Sites (1)

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

• 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.

  PMID: 17084711 BACKGROUND

• 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; Insulin Resistance; Atherosclerosis

Interventions

Chloroquine

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Janet McGill, MD
• Organization: Washington University School of Medicine

jmcgill@wustl.edu

(314) 362-8688

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: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2007
• First Posted: April 3, 2007
• Study Start: September 1, 2004
• Primary Completion: June 1, 2010
• Study Completion: March 1, 2012
• Last Updated: May 10, 2022
• Results First Posted: May 10, 2022

Record last verified: 2022-04

Locations

US (1)