Orlistat for the Treatment of Type I Hyperlipoproteinemia (T1HLP)

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.

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia; Hyperlipoproteinemia Type I
• Intervention / Treatment: Drug: Orlistat

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
• Enrollment (Actual): 2
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390-8537
      • UT Southwestern Medical Center 5323 Harry Hines Blvd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: Alli
NO_INTERVENTION: Off drug; Standard therapy will be given for three months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting Serum Triglycerides	Fasting blood samples were collected on three consequetive days at the end of each three month period. Mean values of the three days were calculated.	3 days

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Abhimanyu Garg, MD, University of Texas

Publications and helpful links

General Publications

• Patni N, Quittner C, Garg A. Orlistat Therapy for Children With Type 1 Hyperlipoproteinemia: A Randomized Clinical Trial. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2403-2407. doi: 10.1210/jc.2018-00369.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (ACTUAL): May 31, 2018
• Study Completion (ACTUAL): December 31, 2022

Study Registration Dates

• First Submitted: May 2, 2016
• First Submitted That Met QC Criteria: May 6, 2016
• First Posted (ESTIMATE): May 10, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 6, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipidemias; Hypertriglyceridemia; Hyperlipoproteinemias; Hyperlipoproteinemia Type I; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lipid Regulating Agents; Anti-Obesity Agents; Orlistat
• Other Study ID Numbers: 012013-042