Orlistat for the Treatment of Type I Hyperlipoproteinemia (T1HLP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02767531
Recruitment Status : Recruiting
First Posted : May 10, 2016
Last Update Posted : June 19, 2017
Information provided by (Responsible Party):
Abhimanyu Garg, University of Texas Southwestern Medical Center

Brief Summary:

Patients with Type I Hyperlipoproteinemia (T1HLP) have a rare form of hypertriglyceridemia marked by significant chylomicronemia and recurrent episodes of acute pancreatitis. T1HLP is caused by a deficiency of lipoprotein lipase or one of its cofactors. Many patients are a challenge to treat, as the only effective therapy available is an extremely low fat diet. This diet is exceedingly difficult to follow, and despite adherence, many patients still have chylomicronemia and develop acute pancreatitis.

Specific Aim: To determine the efficacy of a gastric and pancreatic lipase inhibitor, Orlistat, in reducing serum triglyceride levels in patients with T1HLP.

Condition or disease Intervention/treatment Phase
Hyperlipoproteinemia Type I Hypertriglyceridemia Drug: Orlistat Phase 2

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, Investigator 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.

Investigator will study the efficacy and safety of an inhibitor of intestinal lipase (Orlistat) for reducing serum triglyceride levels in patients with Type I hyperlipoproteinemia. Investigator plan to enroll 20 patients with Type I hyperlipoproteinemia in a randomized, double-blind, placebo-controlled, cross-over trial. 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.

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Orlistat for the Treatment of Type I Hyperlipoproteinemia
Study Start Date : December 2015
Estimated Primary Completion Date : July 31, 2019
Estimated Study Completion Date : July 31, 2019

Arm Intervention/treatment
Experimental: Orlistat
120 mg of Orlistat will be given 3 times to patients weighing greater than 50 kg and patients weighing less than 40 kg will be given 60 mg of Orlistat 3 times a day for 3 months.
Drug: Orlistat
Orlistat is a gastric and pancreatic lipase inhibitor that is approved by the FDA for weight loss. It is available over-the-counter as 60 mg tablets under the trade name Alli, and available by prescription as 120 mg capsules under the trade name Xenical.
Other Name: Alli

No Intervention: Off drug
Standard therapy will be given for three months

Primary Outcome Measures :
  1. Fasting Serum Triglyceride [ Time Frame: 3 months ]
    Fasting blood samples will be collected on three consequetive days at the end of three months period

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Ages Eligible for Study:   8 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Type I hyperlipoproteinemia
  2. Fasting serum triglyceride levels of greater than 1000 mg/dL
  3. Age > 8 years

Exclusion Criteria:

  1. Secondary hypertriglyceridemias due to diabetes, renal disease, hypothyroidism, alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIVprotease inhibitors, retinoic acid derivatives and interferons
  2. Pregnant or lactating women
  3. 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)
  4. Severe anemia (hematocrit < 24%)
  5. Drug use (cocaine, marijuana, LSD, etc.)
  6. Major surgery in the past three months
  7. Congestive heart failure
  8. Serum creatinine greater than 2.5 mg/dL
  9. Cancer within the past five years
  10. Gastrointestinal surgery in the past
  11. Current therapy with anti-coagulants, digoxin, and anti-arrhythmics
  12. Current therapy with cyclosporine
  13. Chronic malabsorption syndromes
  14. Cholestasis
  15. Acute illnesses such as acute pancreatitis in the last 8 weeks

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02767531

Contact: Abhimanyu Garg, MD 214-648-2895
Contact: Claudia Quittner, RN 214-648-9296

United States, Texas
UT Southwestern Medical Center 5323 Harry Hines Blvd Recruiting
Dallas, Texas, United States, 75390-8537
Principal Investigator: Abhimanyu Garg, MD         
Sub-Investigator: Nivedita Patni, M.D.         
Sponsors and Collaborators
University of Texas Southwestern Medical Center
Principal Investigator: Abhimanyu Garg, MD University of Texas

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Abhimanyu Garg, Professor, University of Texas Southwestern Medical Center Identifier: NCT02767531     History of Changes
Other Study ID Numbers: 012013-042
First Posted: May 10, 2016    Key Record Dates
Last Update Posted: June 19, 2017
Last Verified: June 2017

Additional relevant MeSH terms:
Hyperlipoproteinemia Type I
Lipid Metabolism Disorders
Metabolic Diseases
Lipid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Obesity Agents