Diabetic Neuropathy, Hypertriglyceridemia
Conditions
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.
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 Coenzyme A: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 tumor necrosis factor-α. The study is powered to detect differences in microvascular function after 6 months of Lovaza® and differences in ethnic responses.
Interventions
DRUGomega-3-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.
DRUGPlacebo
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.
Sponsors
GlaxoSmithKline
Eastern Virginia Medical School
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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 (aspartate aminotransferase,alanine transaminase, alkaline phosphatase) greater than 3 times the upper limit of normal. 10. Presence of pedal edema. 11. Presence or history of heart failure New York Heart Association 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | One year | 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 |
| Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | One year | 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). |
| Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | One year | Quantitative Sensory Tests (QSTs), including, cold sensation threshold, cold pain threshold and vibration detection threshold, were used to evaluate peripheral sensory perception. |
| Percent Change in Measurements of Indices of Large and Small Fiber Nerve Function Including Vibration Thresholds | One year | 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. |
| Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | One year | Oxidative stress/inflammatory markers (IL1β, IKKβ, TLR4, TNF-α, JNK1, toll-like receptor 2) were assessed through a meal challenge. |
| 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 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 19 |
| 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.
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. | 19 |
| Total | 38 |
Baseline characteristics
| Characteristic | Lovaza | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 58.21 years STANDARD_DEVIATION 1.7 | 59.39 years STANDARD_DEVIATION 1.33 | 60.58 years STANDARD_DEVIATION 2.06 |
| Alkaline phosphatase (u/L) | 70.11 (u/L) STANDARD_DEVIATION 4.4 | 74.63 (u/L) STANDARD_DEVIATION 4.62 | 77.89 (u/L) STANDARD_DEVIATION 6.55 |
| BMI kg/m^2 | 34.37 kg/m^2 STANDARD_DEVIATION 1.83 | 34.10 kg/m^2 STANDARD_DEVIATION 1.11 | 34.04 kg/m^2 STANDARD_DEVIATION 1.17 |
| C-peptide (ng/mL) | 4.56 (ng/mL) STANDARD_DEVIATION 0.45 | 4.61 (ng/mL) STANDARD_DEVIATION 0.3 | 4.66 (ng/mL) STANDARD_DEVIATION 0.4 |
| Fasting glucose (mg/dL) | 157.21 (mg/dL) STANDARD_DEVIATION 12.09 | 156.55 (mg/dL) STANDARD_DEVIATION 7.49 | 155.89 (mg/dL) STANDARD_DEVIATION 9.18 |
| HbA1c (%) | 7.66 % STANDARD_DEVIATION 0.23 | 7.73 % STANDARD_DEVIATION 0.21 | 7.82 % STANDARD_DEVIATION 0.35 |
| HDL cholesterol (mg/dL) | 43.32 (mg/dL) STANDARD_DEVIATION 2.81 | 41.58 (mg/dL) STANDARD_DEVIATION 1.8 | 39.84 (mg/dL) STANDARD_DEVIATION 2.27 |
| Insulin (uIU/mL) | 26.23 (uIU/mL) STANDARD_DEVIATION 5.88 | 32.88 (uIU/mL) STANDARD_DEVIATION 6.96 | 39.54 (uIU/mL) STANDARD_DEVIATION 12.63 |
| LDL cholesterol (mg/dL) | 101.44 (mg/dL) STANDARD_DEVIATION 7.21 | 88.30 (mg/dL) STANDARD_DEVIATION 5.01 | 75.84 (mg/dL) STANDARD_DEVIATION 5.8 |
| Qualifying triglyceride level (mg/dL) | 261.17 mg/dL STANDARD_DEVIATION 50.73 | 237.48 mg/dL STANDARD_DEVIATION 24.42 | 215.05 mg/dL STANDARD_DEVIATION 12.51 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 17 Participants | 34 Participants | 17 Participants |
| serum glutamate oxaloacetate transaminase(AST) (u/L) | 24.11 (u/L) STANDARD_DEVIATION 2.28 | 24.00 (u/L) STANDARD_DEVIATION 8.44 | 22.16 (u/L) STANDARD_DEVIATION 1.5 |
| serum glutamate pyruvate transaminase (ALT) (u/L) | 31.05 (u/L) STANDARD_DEVIATION 3.84 | 30.71 (u/L) STANDARD_DEVIATION 2.2 | 28.79 (u/L) STANDARD_DEVIATION 2.63 |
| Sex: Female, Male Female | 12 Participants | 23 Participants | 11 Participants |
| Sex: Female, Male Male | 7 Participants | 15 Participants | 8 Participants |
| Total cholesterol (mg/dL) | 189.42 (mg/dL) STANDARD_DEVIATION 9.63 | 170.84 (mg/dL) STANDARD_DEVIATION 6.51 | 152.26 (mg/dL) STANDARD_DEVIATION 6.56 |
| Weight (lbs) | 215.16 lbs STANDARD_DEVIATION 10.38 | 215.71 lbs STANDARD_DEVIATION 7.25 | 217.03 lbs STANDARD_DEVIATION 9.62 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 7 / 19 | 8 / 19 |
| serious Total, serious adverse events | 4 / 19 | 2 / 19 |
Outcome results
Primary
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
Time frame: One year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Tibial Nerve Ankle Amplitude | 7.28 uV | Standard Error 0.94 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Tibial Nerve Popliteal Amplitude | 4.08 uV | Standard Error 0.58 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Median Nerve Wrist Amplitude | 6.89 uV | Standard Error 0.6 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Median Nerve Elbow Amplitude | 5.21 uV | Standard Error 0.56 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Peroneal Motor Nerve Ankle Amplitude | 2.97 uV | Standard Error 0.47 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Peroneal Motor Nerve Below Fibular Amplitude | 2.70 uV | Standard Error 0.46 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Peroneal Motor Nerve Above Fibular Amplitude | 2.79 uV | Standard Error 0.46 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Sensory Median Nerve Wrist Amplitude | 22.96 uV | Standard Error 3.04 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Sensory Ulnar Wrist Ampltiude | 26.93 uV | Standard Error 3.39 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Sensory Sural Ankle Ampltiude | 8.01 uV | Standard Error 1.55 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Sensory Median Nerve Wrist Amplitude | 26.56 uV | Standard Error 5.09 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Tibial Nerve Ankle Amplitude | 7.14 uV | Standard Error 1.13 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Peroneal Motor Nerve Below Fibular Amplitude | 2.17 uV | Standard Error 0.32 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Tibial Nerve Popliteal Amplitude | 3.80 uV | Standard Error 0.73 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Sensory Sural Ankle Ampltiude | 8.33 uV | Standard Error 1.83 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Median Nerve Wrist Amplitude | 7.24 uV | Standard Error 0.55 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Peroneal Motor Nerve Above Fibular Amplitude | 2.11 uV | Standard Error 0.31 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Median Nerve Elbow Amplitude | 6.06 uV | Standard Error 0.58 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Sensory Ulnar Wrist Ampltiude | 21.65 uV | Standard Error 5.13 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude. | Peroneal Motor Nerve Ankle Amplitude | 2.55 uV | Standard Error 0.36 |
Primary
Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction
Time frame: One Year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction | Tibial Nerve F-Wave Conduction | 51.14 m/s | Standard Error 3.02 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction | Median Nerve F-Wave Conduction | 29.46 m/s | Standard Error 1.09 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction | Peroneal Motor Nerve F-Wave Conduction | 41.96 m/s | Standard Error 3.09 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction | Tibial Nerve F-Wave Conduction | 55.89 m/s | Standard Error 2.45 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction | Median Nerve F-Wave Conduction | 29.44 m/s | Standard Error 0.9 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction | Peroneal Motor Nerve F-Wave Conduction | 47.47 m/s | Standard Error 2.49 |
Primary
Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency.
Time frame: One Year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Median Nerve Wrist Latency | 4.81 ms | Standard Error 1.15 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Peroneal Motor Nerve Below Fibular Latency | 13.58 ms | Standard Error 0.77 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Tibial Nerve Popliteal Latency | 14.65 ms | Standard Error 0.51 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Peroneal Motor Nerve Above Fibular Latency | 15.37 ms | Standard Error 0.95 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Median Nerve Elbow Latency | 9.16 ms | Standard Error 0.43 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Sensory Median Nerve Wrist Latency | 3.48 ms | Standard Error 0.33 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Tibial Nerve Ankle Latency | 5.08 ms | Standard Error 0.28 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Sensory Ulnar Wrist Latency | 2.51 ms | Standard Error 0.13 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Peroneal Motor Nerve Ankle Latency | 5.77 ms | Standard Error 0.49 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Sensory Sural Ankle Latency | 3.68 ms | Standard Error 0.15 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Peroneal Motor Nerve Ankle Latency | 5.24 ms | Standard Error 0.21 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Tibial Nerve Ankle Latency | 5.29 ms | Standard Error 0.31 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Tibial Nerve Popliteal Latency | 16.41 ms | Standard Error 0.66 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Median Nerve Wrist Latency | 4.56 ms | Standard Error 0.19 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Median Nerve Elbow Latency | 8.79 ms | Standard Error 0.35 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Sensory Sural Ankle Latency | 3.70 ms | Standard Error 0.14 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Peroneal Motor Nerve Below Fibular Latency | 13.20 ms | Standard Error 0.4 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Peroneal Motor Nerve Above Fibular Latency | 14.92 ms | Standard Error 0.45 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Sensory Median Nerve Wrist Latency | 3.01 ms | Standard Error 0.16 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency. | Sensory Ulnar Wrist Latency | 2.62 ms | Standard Error 0.11 |
Primary
Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity.
Time frame: One Year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Peroneal Motor Nerve Abo. Fib. Conduction Velocity | 44.44 m/s | Standard Error 3.65 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Sensory Median Nerve Wrist Conduction Velocity | 43.76 m/s | Standard Error 3.08 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Tibial Nerve Popliteal Conduction Velocity | 41.08 m/s | Standard Error 6.58 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Sensory Ulnar Wrist Conduction Velocity | 46.94 m/s | Standard Error 1.73 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Peroneal Motor Nerve Bel. Fib. Conduction Velocity | 40.36 m/s | Standard Error 1.35 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Sensory Sural Ankle Conduction Velocity | 39.03 m/s | Standard Error 1.61 |
| Placebo | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Median Nerve Elbow Conduction Velocity | 45.89 m/s | Standard Error 1.76 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Sensory Sural Ankle Conduction Velocity | 38.60 m/s | Standard Error 1.57 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Tibial Nerve Popliteal Conduction Velocity | 37.53 m/s | Standard Error 1.51 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Median Nerve Elbow Conduction Velocity | 46.74 m/s | Standard Error 1.23 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Peroneal Motor Nerve Bel. Fib. Conduction Velocity | 39.96 m/s | Standard Error 1.31 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Sensory Median Nerve Wrist Conduction Velocity | 46.59 m/s | Standard Error 1.87 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Sensory Ulnar Wrist Conduction Velocity | 45.22 m/s | Standard Error 1.75 |
| Omega-3-ethyl Esters 4g | Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity. | Peroneal Motor Nerve Abo. Fib. Conduction Velocity | 45.00 m/s | Standard Error 2.89 |
Primary
Efficacy Measures Examining Increased Vascular Response to Ischemic Block and to Local Warming at the Dorsum of the Foot.
Time frame: One Year
Population: Measures of vascular response to ischemic block and local warming at the dorsum of the foot were not reliably collected for this assessment due to the difficulty of analysis and the inability to properly distinguish a vascular response in patients.
Primary
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).
Time frame: One year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Resting sdNN (ms) | 31.924 ms | Standard Error 15.509 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Resting rmsSD (ms) | 28.838 ms | Standard Error 15.592 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Deep Breathing sdNN (ms) | 3.840 ms | Standard Error 10.703 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Deep Breathing rmsSD (ms) | 20.823 ms | Standard Error 2.462 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Valsalva sdNN (ms) | 0.136 ms | Standard Error 0.077 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Valsalva rmsSD (ms) | 12.752 ms | Standard Error 15.511 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Standing sdNN (ms) | 5.3786 ms | Standard Error 10.361 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Standing rmsSD (ms) | 23.725 ms | Standard Error 20.551 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Standing rmsSD (ms) | 38.243 ms | Standard Error 21.85 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Resting sdNN (ms) | 40.748 ms | Standard Error 16.05 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Valsalva sdNN (ms) | 6.333 ms | Standard Error 13.516 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Resting rmsSD (ms) | 72.075 ms | Standard Error 30.165 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Standing sdNN (ms) | 8.622 ms | Standard Error 12.08 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Deep Breathing sdNN (ms) | 11.637 ms | Standard Error 11.426 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Valsalva rmsSD (ms) | 26.668 ms | Standard Error 20.514 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures. | Deep Breathing rmsSD (ms) | 38.136 ms | Standard Error 10.539 |
Primary
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.
Time frame: One year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | IL1β (pg/ml) | 1.13 pg/ml | Standard Error 0.21 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | IKKβ (pg/ml) | 0.98 pg/ml | Standard Error 0.16 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | TLR4 (pg/ml) | 1.11 pg/ml | Standard Error 0.18 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | TNFα (pg/ml) | 1.18 pg/ml | Standard Error 0.19 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | JNK1 (pg/ml) | 0.94 pg/ml | Standard Error 0.15 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | toll-like receptor 2 (pg/ml) | 0.90 pg/ml | Standard Error 0.12 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | JNK1 (pg/ml) | 0.75 pg/ml | Standard Error 0.21 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | IL1β (pg/ml) | 1.14 pg/ml | Standard Error 0.31 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | TNFα (pg/ml) | 0.76 pg/ml | Standard Error 0.11 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | IKKβ (pg/ml) | 0.96 pg/ml | Standard Error 0.17 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | toll-like receptor 2 (pg/ml) | 0.87 pg/ml | Standard Error 0.16 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress. | TLR4 (pg/ml) | 1.17 pg/ml | Standard Error 0.29 |
Primary
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.
Time frame: One year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Sensation Threshold-Finger (°C) | 0.311 °C | Standard Error 0.469 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Pain Threshold-Finger (°C) | -1.167 °C | Standard Error 1.525 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Sesnation Threshold-Toe (°C) | -1.169 °C | Standard Error 1.183 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Pain Threshold-Toe (°C) | 5.658 °C | Standard Error 1.906 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Sensation Threshold-Dorsum (°C) | -2.062 °C | Standard Error 1.484 |
| Placebo | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Pain Threshold-Dorsum (°C) | 0.937 °C | Standard Error 2.215 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Sensation Threshold-Dorsum (°C) | -3.768 °C | Standard Error 1.709 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Sensation Threshold-Finger (°C) | 0.221 °C | Standard Error 0.749 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Pain Threshold-Toe (°C) | -1.405 °C | Standard Error 2.158 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Pain Threshold-Finger (°C) | -1.789 °C | Standard Error 1.882 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Pain Threshold-Dorsum (°C) | -1.739 °C | Standard Error 2.339 |
| Omega-3-ethyl Esters 4g | Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds. | Cold Sesnation Threshold-Toe (°C) | -3.763 °C | Standard Error 1.647 |
Primary
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.
Time frame: One year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change in Measurements of Indices of Large and Small Fiber Nerve Function Including Vibration Thresholds | Vibration Detection Threshold-Finger (% Change) | -0.375 % Change | Standard Error 0.241 |
| Placebo | Percent Change in Measurements of Indices of Large and Small Fiber Nerve Function Including Vibration Thresholds | Vibration Detection Threshold-Toe (% Change) | -3.750 % Change | Standard Error 5.321 |
| Omega-3-ethyl Esters 4g | Percent Change in Measurements of Indices of Large and Small Fiber Nerve Function Including Vibration Thresholds | Vibration Detection Threshold-Finger (% Change) | -1.102 % Change | Standard Error 0.309 |
| Omega-3-ethyl Esters 4g | Percent Change in Measurements of Indices of Large and Small Fiber Nerve Function Including Vibration Thresholds | Vibration Detection Threshold-Toe (% Change) | -8.169 % Change | Standard Error 3.263 |