Clinical trial NCT01675154: Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia
Official title: Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Type 1 Hyperlipoproteinemia
Keywords: hypertriglyceridemia
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2012-08-29
Enrollment: 5
Sex: ALL
Minimum age (years): 12
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: This trial is adaptive design/flexible design. The participants were randomized from the start of the study
Primary purpose: TREATMENT

Brief summary: Funding Source - FDA OOPD

This study is being done to find out whether an investigational (not approved by FDA ) drug called SLx-4090 or Orlistat (FDA approved medication for weight loss) when given alone or in combination can treat the high blood fat (elevated triglycerides)levels found in the condition Type 1 Hyperlipoproteinemia (T1HLP) better or more safely than low fat diet alone, the current standard medical care.

It is also not clear whether Orlistat, that is FDA approved for weight loss, is effective in lowering blood fat levels in patients with Type 1 hyperlipoproteinemia (T1HLP). The researchers are interested in learning whether any one of these drugs when given alone or in combination is more effective and safe in treating T1HLP.

Detailed description: Type I hyperlipoproteinemia is a rare, autosomal recessive metabolic disorder characterized by extreme hypertriglyceridemia due to a deficiency in lipoprotein lipase or related proteins. Treatment of these patients is challenging as triglyceride-lowering medications are ineffective. A low fat diet is helpful, however, despite good dietary compliance, some patients continue to have severe hypertriglyceridemia and recurrent pancreatitis which can be life threatening. Therefore, we wish to investigate whether inducing dietary fat malabsorption or inhibiting chylomicron formation will cause further lowering of serum triglycerides (TG) beyond the effect of limiting dietary fat intake.

We will study the efficacy and safety of an inhibitor of intestinal lipase (Orlistat) and an intestinal-specific inhibitor of microsomal triglyceride transport protein (MTP) involved in the assembly and secretion of chylomicrons (SLx-4090), alone and in combination, for reducing serum triglyceride levels in patients with Type I hyperlipoproteinemia. We plan to enroll 20 patients with Type I hyperlipoproteinemia in a randomized, double-blind, placebo-controlled, cross-over trial. After a baseline evaluation, the subjects will be randomly assigned to placebo/placebo, Orlistat/placebo, SLx-4090/placebo or Orlistat/SLx-4090 for the duration of four weeks followed by a one week wash out period. During the last week of each study period, fasting blood samples will be drawn for three consecutive days for serum lipids and chemistry panel. The primary endpoint will be serum triglycerides; the secondary endpoint variables will be fasting and postprandial serum chylomicron-TG levels, postprandial serum TG levels during a meal tolerance test and retinyl palmitate levels during a meal tolerance test. Repeated measures analysis of variance will be used for statistical comparisons.

Our results may help in designing novel therapeutic approaches for patients with Type 1 hyperlipoproteinemia.

Eligibility criteria: Inclusion Criteria:

* Type I hyperlipoproteinemia.
* Fasting serum triglyceride levels of greater than 1000 mg/dL.
* Age \> 12 years

Exclusion Criteria:

* Secondary hypertriglyceridemias due to diabetes, renal disease, hypothyroidism, alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-protease inhibitors, retinoic acid derivatives and interferons.
* 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 for men or 168 g per week for men)
* 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

Primary outcomes:
measure: Serum Triglycerides at First Intervention Period
timeFrame: 4 weeks after the assigned treatment (first intervention period)
measure: Serum Triglycerides at Second Intervention Period
timeFrame: 4 weeks after the assigned treatment (Second Intervention Period)
measure: Serum Triglycerides at Third Intervention Period
timeFrame: 4 weeks after the assigned treatment (Third Intervention Period)
measure: Serum Triglycerides at Fourth Intervention Period
timeFrame: 4 weeks after the assigned treatment (Fourth Intervention Period)
Secondary outcomes:
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center 5323 Harry Hines Blvd
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Abhimanyu Garg, MD
role: PRINCIPAL_INVESTIGATOR
References: