Lovaza® and Microvascular Function in Type 2 Diabetes

NCT00931879 | Completed Phase 4 Results

• 1 other identifier: LVZ111903
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertriglyceridemia; Diabetic Neuropathy

Outcome Measures

Primary Outcomes (9)

• Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude.

  19 participants in each arm( placebo or omega-3-ethyl esters 4g) were analyzed . Conduction velocities and amplitude of the following nerves were compared between each arm: Tibial Nerve Ankle Amplitude, Tibial Nerve Popliteal Amplitude, Median Nerve Wrist Amplitude, Median Nerve Elbow Amplitude, Peroneal Motor Nerve Ankle Amplitude, Peroneal Motor Nerve Below Fibular Amplitude, Peroneal Motor Nerve Above Fibular Amplitude, Sensory Median Nerve Wrist Amplitude, Sensory Ulnar, Sensory Sural Ankle Ampltiude Wrist Ampltiude

  One year

• Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures.

  Quantitative Autonomic Function Tests (QAFTs) were performed. Primarily, power spectral analysis of heart rate variability (HRV) and time- and frequency-domain analyses, including measures of the sympathetic and parasympathetic control of the heart beat (R-R interval), were recorded with deep breathing, Valsalva, and standing from the sitting position maneuvers. Additionally, the sample difference of the beat to beat (NN) intervals and the TSP was calculated as well as the standard deviation of all normal R-R intervals (sdNN).

  One year

• Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds.

  Quantitative Sensory Tests (QSTs), including, cold sensation threshold, cold pain threshold and vibration detection threshold, were used to evaluate peripheral sensory perception.

  One year

• Percent Change in Measurements of Indices of Large and Small Fiber Nerve Function Including Vibration Thresholds

  Quantitative Sensory Tests (QSTs), including vibration detection threshold, were used to evaluate peripheral sensory perception. Mean represents percent change of total group. Measurements taken at baseline and at one year.

  One year

• Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress.

  Oxidative stress/inflammatory markers (IL1β, IKKβ, TLR4, TNF-α, JNK1, toll-like receptor 2) were assessed through a meal challenge.

  One year

• Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity.

  One Year

• Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency.

  One Year

• Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction

  One Year

• Efficacy Measures Examining Increased Vascular Response to Ischemic Block and to Local Warming at the Dorsum of the Foot.

  One Year

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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: Placebo

omega-3-ethyl esters 4g

ACTIVE COMPARATOR

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-ethyl esters

Interventions

omega-3-ethyl esters DRUG

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.

Also known as: Lovaza

omega-3-ethyl esters 4g

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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).
• Presence of diabetic retinopathy that is more severe than "background" level.
• Presence of diabetic nephropathy, defined by urine dipstick results greater than 300 mg/100 mL for protein (proteinuria).
• Presence of clinically significant neuropathy that is clearly of non-diabetic origin, e.g. alcoholic or autoimmune.
• Bilateral amputation of lower extremities or foot ulcers involving the great toes. Presence of neuroarthropathy (Charcot deformity) is allowable.
• History of major macrovascular events such as myocardial infarction or stroke.
• Participation in another clinical trial concurrently or within 30 days prior to entry into this study.
• 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.
• Patients with moderate or severe hepatic insufficiency or abnormalities of liver function defined as any liver enzymes (aspartate aminotransferase,alanine transaminase, alkaline phosphatase) greater than 3 times the upper limit of normal.
• Presence of pedal edema.
• Presence or history of heart failure New York Heart Association Class II or greater.
• Other serious medical conditions that in the opinion of the investigator, would compromise the subject's participation in the study.
• Concomitant use of medications known to exacerbate triglyceride levels, such as estrogens.

Sponsors & Collaborators

• Eastern Virginia Medical School: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Strelitz Diabetes Center

Norfolk, Virginia, 23510, United States

Location

MeSH Terms

Conditions

Hypertriglyceridemia; Diabetic Neuropathies

Interventions

Omacor

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Results Point of Contact

• Title: Dr. Henri Parson
• Organization: Eastern Virginia Medical School

parsonhk@evms.edu

(757)446-7976

Study Officials

• Aaron I Vinik, MD, PhD

  Eastern Virginia Medical School

  PRINCIPAL INVESTIGATOR

• Henri K Parson, PhD

  Eastern Virgina Medical School

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 17, 2009
• First Posted: July 2, 2009
• Study Start: October 1, 2009
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: May 9, 2017
• Results First Posted: May 9, 2017

Record last verified: 2017-03

Locations

US (1)