Orlistat for the Treatment of Type I Hyperlipoproteinemia

NCT ID: NCT02767531

Last Updated: 2023-02-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2022-12-31

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.

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.

Conditions

Hyperlipoproteinemia Type I; Hypertriglyceridemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Orlistat

Intervention Type: DRUG

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.

Off drug

Standard therapy will be given for three months

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Alli

Eligibility Criteria

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

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Texas Southwestern Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Abhimanyu Garg

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Abhimanyu Garg, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas

Locations

UT Southwestern Medical Center 5323 Harry Hines Blvd

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 29659879 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

012013-042

Identifier Type: -

Identifier Source: org_study_id