Phase 2 Study of Orlistat and SLx-4090 for the Treatment of Type 1 Hyperlipoproteinemia
| Status: | Recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 12 - 100 |
| Updated: | 10/14/2018 |
| Start Date: | November 2015 |
| End Date: | July 31, 2019 |
| Contact: | Claudia Quittner, RN, BSN, MS |
| Email: | claudia.quittner@utsouthwestern.edu |
| Phone: | 214-648-9296 |
Phase 2 Study of Orlistat and SLx-4090 for Teh Treatment of Type 1 Hyperlipoproteinemia
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.
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.
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.
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.
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
We found this trial at
2
sites
Dallas, Texas 75390
Principal Investigator: Abhimanyu Garg, MD
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2201 Inwood Rd
Dallas, Texas 75235
Dallas, Texas 75235
(214) 645-8300
Phone: 214-648-9296
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