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Lovaza® and Microvascular Function in Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Aaron I. Vinik, MD, PhD, Eastern Virginia Medical School
ClinicalTrials.gov Identifier:
NCT00931879
First received: June 17, 2009
Last updated: August 14, 2012
Last verified: August 2012
History of Changes
  Purpose

The objective of this study is to determine the efficacy of 6 months of 4 g/day oral Lovaza® on endothelial-dependent and heat-induced vasodilation in type 2 diabetics with neuropathy and elevated triglyceride levels. Omega-3 fatty acids appear to exert beneficial effects on vascular function that are independent of the changes in serum triglycerides. The efficacy will be compared with a placebo given at the same duration. Efficacy of the drug will be evaluated after 3 and 6 months of treatment. This timeline should be adequate for evaluation of the primary neurophysiological endpoints. Previously, the investigators have demonstrated that it is feasible to pharmacologically alter nerve fiber density in as little as 18 weeks and that this correlates with subjective and objective measures of neurovascular function. The investigators are predicting an enhancement of post-ischemic hyperemia of the foot dorsum, where the dilative mechanism is primarily endothelium-dependent and a similar improvement in heat-induced hyperemia.


Condition Intervention Phase
Hypertriglyceridemia
Diabetic Neuropathy
 Drug: omega-3-acie ethyl esters
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: The Role of Lovaza® on Microvascular Function and Lipoprotein Profile in Type 2 Diabetes

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Eastern Virginia Medical School:

Primary Outcome Measures:
  • Efficacy measures are nerve conduction studies, specifically increases in conduction velocity and increased vascular response to ischemic block and to local warming at the dorsum of the foot. [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Measurements of indices of large and small fiber nerve function include: vibration and thermal thresholds, heart rate variation, markers of inflammation, oxidative stress, dyslipidemia and diabetes control [ Time Frame: One year ] [ Designated as safety issue: No ]

Enrollment: 44
Study Start Date: October 2009
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Subjects are males or non-pregnant, non-lactating females age 18-80 years. All subjects must have been diagnosed with type 2 diabetes mellitus a minimum of two years according to the current ADA criteria and triglyceride levels above 149 mg/dL. Subjects in this arm will be taking placebo for 6 months.
 Drug: omega-3-acie ethyl esters
Lovaza (TM) (omega-3-ethyl esters) 1 gram Capsules are indicated as an adjunct to diet to reduce very high (>500 mg/dL) triglyceride (TG) levels in adult patients.
Other Names:
  • Lovaza
  • omega-3-ethyl esters
Active Comparator: Lovaza
Subjects are males or non-pregnant, non-lactating females age 18-80 years. All subjects must have been diagnosed with type 2 diabetes mellitus a minimum of two years according to the current ADA criteria and triglyceride levels above 149 mg/dL. Subjects in this arm will be taking 4 g of Lovaza per day for 6 months.
 Drug: omega-3-acie ethyl esters
Lovaza (TM) (omega-3-ethyl esters) 1 gram Capsules are indicated as an adjunct to diet to reduce very high (>500 mg/dL) triglyceride (TG) levels in adult patients.
Other Names:
  • Lovaza
  • omega-3-ethyl esters

Detailed Description:

This pilot study is a within-subject repeated measures design. This study will compare the neurophysiological and vascular responses to placebo and treatment with Lovaza® (omega-3-acid ethyl esters, Reliant Pharmaceuticals, Inc.) in subjects with type 2 diabetes, neuropathy, and dyslipidemia.

Lovaza's potential mechanism of action is the inhibition of acyl CoA:1, 2-diacylglycerol acyltransferase and increased peroxisomal β-oxidation in the liver.

Subjects will be recruited and a baseline of physiological, neurological and hematological profile established for each patient. Forty-four subjects (20 in the active arm, 20 in the placebo arm, and 2 replacements for each arm) will receive 4 g/day Lovaza® tablets or placebo for a period of 6 months. All subjects will receive a physical and neurological exam as well as neurovascular function testing. This includes nerve conduction studies, quantitative sensory testing, quantitative autonomic testing, and skin blood flow testing, which includes, ischemia reperfusion. Lab tests include an insulin resistance profile, hepatic and renal function profiles, lipid profile, C-reactive protein, thyroid stimulating hormone, and fatty acids. Other tests include inflammatory markers such as adiponectin and TNF-α. The study is powered to detect differences in microvascular function after 6 months of Lovaza® and differences in ethnic responses.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects may be males or non-pregnant, non-lactating females age 18-80 years.
  2. Subjects must have been diagnosed with type 2 diabetes mellitus according to the current ADA criteria.
  3. Triglyceride levels above 149 mg/dL
  4. Minimum of 2 years after diagnosis of type 2 diabetes
  5. Prior to participation in this study, each subject must sign an informed consent document.

Exclusion Criteria:

  1. Presence of type 1 diabetes mellitus (defined as C-peptide < 1 ng/ml or diabetes onset at < 35 years of age in a non-obese patient).
  2. Presence of diabetic retinopathy that is more severe than "background" level.
  3. Presence of diabetic nephropathy, defined by urine dipstick results greater than 300 mg/100 mL for protein (proteinuria).
  4. Presence of clinically significant neuropathy that is clearly of non-diabetic origin, e.g. alcoholic or autoimmune.
  5. Bilateral amputation of lower extremities or foot ulcers involving the great toes. Presence of neuroarthropathy (Charcot deformity) is allowable.
  6. History of major macrovascular events such as myocardial infarction or stroke.
  7. Participation in another clinical trial concurrently or within 30 days prior to entry into this study.
  8. The use of ACE-inhibiting agents or angiotensin receptor blockade therapy (ARB) is allowed but must have been stable for at least 30 days prior to study entry and may not change during the course of the study. This is prudent due to their potential effects on blood flow.
  9. Patients with moderate or severe hepatic insufficiency or abnormalities of liver function defined as any liver enzymes (AST, ALT, alkaline phosphatase) greater than 3 times the upper limit of normal.
  10. Presence of pedal edema.
  11. Presence or history of heart failure NYHA Class II or greater.
  12. Other serious medical conditions that in the opinion of the investigator, would compromise the subject's participation in the study.
  13. Concomitant use of medications known to exacerbate triglyceride levels, such as estrogens.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00931879

Locations
United States, Virginia
Strelitz Diabetes Center
Norfolk, Virginia, United States, 23510
Sponsors and Collaborators
Eastern Virginia Medical School
GlaxoSmithKline
Investigators
Principal Investigator: Aaron I Vinik, MD, PhD Eastern Virginia Medical School
Study Director: Henri K Parson, PhD Eastern Virgina Medical School
  More Information

No publications provided

Responsible Party: Aaron I. Vinik, MD, PhD, Principal Investigator, Eastern Virginia Medical School
ClinicalTrials.gov Identifier: NCT00931879     History of Changes
Other Study ID Numbers: LVZ111903
Study First Received: June 17, 2009
Last Updated: August 14, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetic Neuropathies
Hypertriglyceridemia
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
 Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders

ClinicalTrials.gov processed this record on May 16, 2013