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Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia

Phase 2
Recruiting
Conditions
Type 1 Hyperlipoprotenemia
Interventions
Drug: Placebo
Registration Number
NCT05816343
Lead Sponsor
University of Texas Southwestern Medical Center
Brief Summary

Type I hyperlipoproteinemia (T1HLP, also known as familial chylomicronemia syndrome or FCS) is a rare diseasewhere the blood triglycerides (fats) are very high. It is caused by lack of certain enzymes and proteins in the bodythat are important in disposing circulating fats from blood. Treatment of T1HLP patients who have very high levels of blood fats (≥ 1,000 mg/dL) is challenging as conventional triglyceride-lowering medications, such as fibrates and fishoil, are ineffective.

The purpose of this trial is to study the long-term efficacy and safety of orlistat for reducing blood triglyceride levels in patients with T1HLP.

Detailed Description

The hypotheses to be tested and the specific aims are:

Hypothesis 1: As compared to placebo, Orlistat will be effective and safe in lowering fasting serum TG concentrations in patients with T1HLP.

Specific Aim 1: To investigate the efficacy and safety of Orlistat for reducing fasting serum TG levels in 28 patients with T1HLP in a double-blind, randomized, placebo-controlled, parallel design study for a period of 24 weeks.

Hypothesis 2: The efficacy and safety of Orlistat in patients with T1HLP will be maintained over a period of up to 48 weeks.

Specific Aim 2: To investigate the efficacy and safety of Orlistat in patients with T1HLP in an open-label extension study for a period of up to 48 weeks-.

After a screening evaluation, the subjects will be advised to consume an extremely low fat diet (≤15% of total energy from fat) for the entire duration of the study. After the baseline period of 8 weeks, they will be randomly assigned to placebo or Orlistat for the duration of 24 weeks (Phase 1). After Phase 1, all patients will enter an open-label extension (Phase 2) and receive Orlistat for a period of 24 weeks for a total study duration of 56 weeks. During the last week of Baseline Period, Phase 1, and Phase 2, blood lipids and chemistry panel will be analyzed for three consecutive days, and fat-soluble vitamin levels will be measured once. All the visits are going to be outpatient.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
28
Inclusion Criteria

Not provided

Exclusion Criteria
  • Secondary hypertriglyceridemia due to diabetes, renal disease, , alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-1 protease inhibitors, retinoic acid derivatives, interferons, or lasparaginase.
  • On lomitapide or participating in clinical trial of volanesorsen and olezarsen
  • On cyclosporine
  • Having serum TSH outside of the normal range if on levothyroxine supplementation.
  • Use of levothyroxine to suppress TSH in individuals with thyroid cancer.
  • Pregnant or lactating women
  • Significant liver disease (elevated transaminases > 2 times upper limit of normal)
  • Alcohol abuse (> 7 drinks or 84 g per week for women and > 14 drinks or 168 g per week for men)
  • Severe anemia (hematocrit < 24%)
  • Illicit drug use (cocaine, marijuana, LSD, etc.)
  • Major surgery in the past three months
  • Congestive heart failure
  • Serum creatinine greater than 2.5 mg/dL
  • Cancer within the past five years
  • Gastrointestinal surgery in the past
  • Current therapy with anti-coagulants, digoxin and anti-arrhythmics
  • Chronic malabsorption syndromes
  • Cholestasis
  • Acute illnesses such as acute pancreatitis in the last 8 weeks
  • Previous history of renal calcium oxalate stones

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo will be given orally.
Orlistat DrugOrlistatDrug will be given orally.
Primary Outcome Measures
NameTimeMethod
Change in Triglycerides24 weeks

Change in fasting serum TG levels weeks compared to the baseline fasting serum TG levels .

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

UT southwestern Medical Center

🇺🇸

Dallas, Texas, United States

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