Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia

Type 1 Hyperlipoproteinemia Clinical Trial

Official title:

Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01675154
• Other study ID #: 3940
• Secondary ID: FD-R-003940
• Status: Terminated
• Phase: Phase 2
• Start date: November 2015
• Est. completion date: June 30, 2020

Study information

• Verified date: July 2021
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: June 30, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Hyperlipidemias
• Hyperlipoproteinemias
• Type 1 Hyperlipoproteinemia

Intervention

Drug:
• SLx-4090 placebo
Given for 4 weeks
• Orlistat Placebo
Given for 4 weeks
• Orlistat
Given for 4 weeks
• Slx-4090
Given for 4 weeks

Locations

Country	Name	City	State
United States	UT Southwestern Medical Center	Dallas	Texas
United States	UT Southwestern Medical Center 5323 Harry Hines Blvd	Dallas	Texas

Sponsors (1)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Triglycerides at First Intervention Period	Serum triglyceride level will be measured after taking each assigned intervention at first intervention period.	4 weeks after the assigned treatment (first intervention period)
Primary	Serum Triglycerides at Second Intervention Period	Serum triglyceride level will be measured after taking each assigned intervention at second intervention period	4 weeks after the assigned treatment (Second Intervention Period)
Primary	Serum Triglycerides at Third Intervention Period	Serum triglyceride level will be measured after taking each assigned intervention at intervention period	4 weeks after the assigned treatment (Third Intervention Period)
Primary	Serum Triglycerides at Fourth Intervention Period	Serum triglyceride level will be measured after taking each assigned intervention at fourth intervention period	4 weeks after the assigned treatment (Fourth Intervention Period)