Carnitine for the Treatment of Atherosclerosis.

NCT02117661 | Completed Phase 2 DMC

• 1 other identifier: L-Carnitine-01
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 2

Brief Summary

Obesity is one of the main causes of the metabolic syndrome, a condition which is becoming more common in Canada and worldwide. Metabolic syndrome is a name for a group of heart disease risk factors that occur together: obesity, diabetes, high blood pressure, and high cholesterol. These patients have a high risk of developing narrowing and blockages of blood vessels which occur when fat and cholesterol build up in the walls of blood vessels and form plaque. This is called atherosclerosis. Plaque buildup leads to stroke, heart attacks, and death. We do not understand the underlying mechanisms of the metabolic syndrome and we do not have a treatment for it. L-carnitine, a dietary supplement, has been shown to treat some components of the metabolic syndrome, but its benefit to reduce plaque in the blood vessels has never been studied. Recently there has been some controversy because a new study showed that L-carnitine could make heart disease worse in some patients. Our goal is to study whether supplementation with L-carnitine does in fact prevent or reduce buildup of plaque in blood vessels of patients with the metabolic syndrome. This novel therapy has the potential to decrease the burden of heart disease in obese and diabetic patients with the metabolic syndrome.

Conditions

Metabolic Syndrome

Keywords

L-carnitine; Metabolic syndrome; Atherosclerosis; Coronary artery disease; Carotid; Plaque; Cardiovascular disease; Heart disease; Vascular disease

Outcome Measures

Primary Outcomes (1)

• Change in carotid Total Plaque Volume

  Carotid 3D ultrasound scan

  Six months

Secondary Outcomes (1)

• Change in LDL size profile

  Six months

Study Arms (2)

L-carnitine capsules

EXPERIMENTAL

2000 mg daily (2x 500 mg capsules twice a day - BID) for six months

Dietary Supplement: L-carnitine capsules

Cellulose capsules

PLACEBO COMPARATOR

2x capsules twice a day - BID (4 total per day) for six months

Dietary Supplement: Cellulose capsules

Interventions

L-carnitine capsules DIETARY_SUPPLEMENT

Oral

Also known as: levocarnitine, carnitor

L-carnitine capsules

Cellulose capsules DIETARY_SUPPLEMENT

oral

Cellulose capsules

Eligibility Criteria

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

You may qualify if:

• STEP 1: Initial screening; BP, weight and fasting blood samples will be obtained.
• Men and women, \>18 years, meeting the criteria for clinical diagnosis of MetS, according to the International Diabetes Federation (IDF) harmonized definition, where any 3 of the 5 following risk factors cut points constitutes a diagnosis of MetS:
• Elevated waist circumference: Population- and country-specific definitions; Health Canada recommends males 102 cm and women 88cm.
• Elevated triglycerides: 150 mg/dL (1.7 mmol/L).
• Reduced HDL: 40 mg/dL (1.0 mmol/L) in males; 50 mg/dL (1.3 mmol/L) in females or treated.
• Elevated BP: Systolic 130 and/or diastolic 85 mm Hg or treated.
• Elevated fasting glucose: 100 mg/dL (5.6 mmol/L), or HbA1c ≥6.2%, or treated.
• Willing to provide informed consent. STEP 2: Baseline plaque volume ≥50 mm3 by 3D US, to ensure sufficient detectable plaque. This will be measured after consent (at Step 1), but prior to randomization/enrolment (Step 2).

You may not qualify if:

• Individuals who have had a change in statin and/or diabetes medication therapy or dosing in the last three months;
• Who are actively having an unstable arrhythmia, angina or heart attack (untreated and/or unstable patients): symptomatic heart failure (NYHA 2 or greater); renal failure (GFR \<50 mL/min/1.73m2);
• Known severe abnormal blood biochemistries: Na \<100 or \>150 mmol/L, K \<2 or \>5 mmol/L, Total Serum Ca \>3 mmol/L;
• Known severe liver disease: AST \>100 U/L, ALT \>80 U/L, or a diagnosis of cirrhosis (Child Pugh Class A to C);
• Known severe anemia: HgB \<70 g/L;
• Have endocrine disorders, e.g. Cushing's disease, hyper- or hypo-thyroidism;
• Any condition expected to limit survival to less than six (6) months (ex. malignant tumor);
• A condition limiting adherence to study procedure (i.e. alcoholism, drug addiction, known poor adherence, severe mental disorder);
• Concomitant treatment with: anticonvulsants; L-C or derivatives; Acenocoumarol (Sintrom) and Warfarin (Coumadin) anticoagulants and vitamin K antagonists; \>1g fish oil; and/or thyroid treatment;
• A seizure disorder or at risk of seizure (CNS mass or medications that lower seizure threshold); receiving treatments for cancer or HIV infection (secondary L-C deficiency);
• Currently pregnant or breastfeeding;
• A history of allergy or intolerance to L-C or derivatives;
• Vegetarians (do not eat animal flesh) due to potential for altered L-C metabolism;
• Patients who have had a carotid surgery (ie. endarterectomy (CEA) or stent) or who are scheduled to receive carotid surgery during the trial.

Sponsors & Collaborators

• Dr. Amer Johri: lead
• Heart and Stroke Foundation of Canada: collaborator
• Queen's University: collaborator

Study Sites (2)

Queen's University, Cardiovascular Imaging Network at Queen's (CINQ), Kingston General Hospital

Kingston, Ontario, K7L 3N6, Canada

Location

Robarts Institute, Stroke Prevention & Atherosclerosis Research Centre (SPARC)

London, Ontario, N6G 2V2, Canada

Location

Related Publications (1)

• Johri AM, Hetu MF, Heyland DK, Herr JE, Korol J, Froese S, Norman PA, Day AG, Matangi MF, Michos ED, LaHaye SA, Saunders FW, Spence JD. Progression of atherosclerosis with carnitine supplementation: a randomized controlled trial in the metabolic syndrome. Nutr Metab (Lond). 2022 Apr 2;19(1):26. doi: 10.1186/s12986-022-00661-9.

  PMID: 35366920 DERIVED

Related Links

• Cardiovascular Imaging Network at Queen's (CINQ)

MeSH Terms

Conditions

Metabolic Syndrome; Atherosclerosis; Coronary Artery Disease; Plaque, Amyloid; Cardiovascular Diseases; Heart Diseases; Vascular Diseases

Interventions

Carnitine; Cellulose

Condition Hierarchy (Ancestors)

Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Myocardial Ischemia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines; Organic Chemicals; Glucans; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Amer M Johri, MD

  Queen's University

  PRINCIPAL INVESTIGATOR

• J.David Spence, MD

  Robarts Institute

  PRINCIPAL INVESTIGATOR

• Daren K Heyland, MD

  Queen's University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: April 16, 2014
• First Posted: April 21, 2014
• Study Start: January 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: May 1, 2019
• Last Updated: June 26, 2020

Record last verified: 2018-11

Locations

CA (2)