Hypertriglyceridemia
Conditions
Brief summary
High triglyceride levels are increasingly recognized in children, particularly those who are overweight. There are no studies of treatment of high triglycerides in children and adolescents. Fish oil is attractive because it is considered safe and effective for treating high triglycerides in adults and has been used safely for other purposes in children. The investigators will conduct a randomized study of Lovaza (the only prescription omega-3 fish oil medication) in 44 children and adolescents to study efficacy in lowering triglycerides, safety, and possible mechanisms of beneficial effects.
Detailed description
Participants (n = 42, age 14 + 2 yrs) with hypertriglyceridemia and LDL cholesterol \< 160 mg/dl were enrolled in a randomized double blind cross over trial comparing 4 g fish oil daily with placebo. Treatment interval was 8 weeks with a 4 week wash out, between the two treatment intervals. Lipid profile, lipoprotein particle distribution and size, glucose, insulin, high sensitivity C reactive protien (CRP), interleukin-6, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and thrombin generation were measured. Patients were evaluated at 6 time points: Visit 1/baseline (week 0), Visit 2/randomization (week 4), Visit 3/after treatment 1 (week 12) , Visit 4/after wash out (week 16), Visit 5/after treatment 2 (week 24) and Visit 6/close out (week 28) . Patients were advised to maintain a stable diet and not alter baseline fish consumption . One participant took an oral contraceptive throughout the trial. Any fish oil supplements were discontinued. Advice on a heart healthy diet was provided. Blood pressure (right arm sitting with appropriate sized cuff, taken 3 times, last measurement used), height, and weight were measured at the beginning of the study, after the first wash out period, and close out. Participant phone contact was made during each treatment arm to assess diet stability. Fasting lipid profile was performed at every visit. Red blood cell fatty acid profile and secondary endpoints were performed at all visits except baseline.
Interventions
Omega-3-acid ethyl esters (Lovaza), two 1-gram capsules taken twice daily for 8 weeks
DRUGPlacebo
Placebo (corn oil), two 1-gram capsules taken twice daily for 8 weeks
Sponsors
GlaxoSmithKline
Johns Hopkins University
Thomas Jefferson University
Babu Balagopal
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients who are 10-17 years of age * Fasting triglyceride level \>150 mg/dl and \< 750 mg/dl measured on 2 separate occasions. * Ability to follow the study procedures and adhere to the diet counseling recommendations * Written parental permission and assent are obtained prior to any research procedures
Exclusion criteria
* Bleeding disorders * Diabetes mellitus (impaired glucose tolerance is not an exclusion) * Uncontrolled hypothyroidism * Liver disease * Allergy to fish/shellfish * Patients requiring chronic use of aspirin and non-steroidal anti-inflammatory agents * Patients requiring lipid lowering agents * LDL-Cholesterol levels \>160 mg/dl * Current participation in another clinical study or within the previous 30 days * Alcohol use * Currently pregnant or planning to become pregnant during the course of this trial (confirmed by pregnancy testing) * Any significant medical condition which the investigator believes would interfere with the patient's ability to safely participate in this trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Triglyceride Level | after 8 week treatment or placebo period |
Countries
United States
Participant flow
Recruitment details
Patients were recruited from Nemours Alfred I. duPont Hospital for Children, Johns Hopkins University and Thomas Jefferson University. Recruitment took place between July 2009 and December 2011.
Pre-assignment details
Patients completed a 4 week dietary run-in prior to randomization at visit 2.
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Lovaza) Followed by Placebo Omega-3-acid ethyl esters (Lovaza) two 1-gram capsules taken twice daily for 8 weeks followed by placebo for 8 weeks | 20 |
| Placebo Followed by Treatment (Lovaza) Placebo, two 1-gram capsules (corn oil) taken twice daily for 8 weeks followed by treatment (Lovaza) for 8 weeks | 22 |
| Total | 42 |
Baseline characteristics
| Characteristic | Placebo Followed by Treatment (Lovaza) | Treatment (Lovaza) Followed by Placebo | Total |
|---|---|---|---|
| Age, Continuous | 14.2 years STANDARD_DEVIATION 0.5 | 14 years STANDARD_DEVIATION 0.4 | 14.1 years STANDARD_DEVIATION 0.5 |
| Region of Enrollment United States | 22 participants | 20 participants | 42 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 14 Participants | 15 Participants | 29 Participants |
| Triglyceride (mg/dL | 280 mg/dL STANDARD_DEVIATION 25 | 260 mg/dL STANDARD_DEVIATION 22 | 270 mg/dL STANDARD_DEVIATION 24 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 20 | 0 / 20 | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 20 | 0 / 20 | 0 / 22 | 1 / 22 |
Outcome results
Primary
Change in Triglyceride Level
Time frame: after 8 week treatment or placebo period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Omega-3-acid Ethyl Esters (Lovaza) | Change in Triglyceride Level | -52 mg/dL | Standard Deviation 16 |
| Placebo | Change in Triglyceride Level | -16 mg/dL | Standard Deviation 15 |