Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia

NCT ID: NCT05816343

Last Updated: 2025-05-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-26
• Study Completion Date: 2029-05-30

Brief Summary

Type I hyperlipoproteinemia (T1HLP, also known as familial chylomicronemia syndrome or FCS) is a rare diseasewhere the blood triglycerides (fats) are very high. It is caused by lack of certain enzymes and proteins in the bodythat are important in disposing circulating fats from blood. Treatment of T1HLP patients who have very high levels of blood fats (≥ 1,000 mg/dL) is challenging as conventional triglyceride-lowering medications, such as fibrates and fishoil, are ineffective.

The purpose of this trial is to study the long-term efficacy and safety of orlistat for reducing blood triglyceride levels in patients with T1HLP.

Detailed Description

The hypotheses to be tested and the specific aims are:

Hypothesis 1: As compared to placebo, Orlistat will be effective and safe in lowering fasting serum TG concentrations in patients with T1HLP.

Specific Aim 1: To investigate the efficacy and safety of Orlistat for reducing fasting serum TG levels in 28 patients with T1HLP in a double-blind, randomized, placebo-controlled, parallel design study for a period of 24 weeks.

Hypothesis 2: The efficacy and safety of Orlistat in patients with T1HLP will be maintained over a period of up to 48 weeks.

Specific Aim 2: To investigate the efficacy and safety of Orlistat in patients with T1HLP in an open-label extension study for a period of up to 48 weeks-.

After a screening evaluation, the subjects will be advised to consume an extremely low fat diet (≤15% of total energy from fat) for the entire duration of the study. After the baseline period of 8 weeks, they will be randomly assigned to placebo or Orlistat for the duration of 24 weeks (Phase 1). After Phase 1, all patients will enter an open-label extension (Phase 2) and receive Orlistat for a period of 24 weeks for a total study duration of 56 weeks. During the last week of Baseline Period, Phase 1, and Phase 2, blood lipids and chemistry panel will be analyzed for three consecutive days, and fat-soluble vitamin levels will be measured once. All the visits are going to be outpatient.

Conditions

Type 1 Hyperlipoprotenemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: TRIPLE

Study Groups

Orlistat Drug

Drug will be given orally.

Group Type: ACTIVE_COMPARATOR

Orlistat

Intervention Type: DRUG

Orlistat is an inhibitor of gastric and pancreatic lipases and can reduce dietary fat absorption by 30%. Orlistat at a dose of 2 capsules (each containing 60 mg of active drug) three times a day with each meal (a total dose of 360 mg daily).

Placebo

Placebo will be given orally.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo at a dose of 2 capsules (each containing 60 mg placebo) three times a day with each meal (a total dose of 360 mg daily).

Interventions

Orlistat

Orlistat is an inhibitor of gastric and pancreatic lipases and can reduce dietary fat absorption by 30%. Orlistat at a dose of 2 capsules (each containing 60 mg of active drug) three times a day with each meal (a total dose of 360 mg daily).

Intervention Type: DRUG

Placebo

Placebo at a dose of 2 capsules (each containing 60 mg placebo) three times a day with each meal (a total dose of 360 mg daily).

Intervention Type: DRUG

Other Intervention Names

Alli

Eligibility Criteria

Inclusion Criteria

• Age ≥ 8 years
• Well controlled diabetes mellitus with hemoglobin A1c < 8%
• Off orlistat for a period of 2 months

Exclusion Criteria

• Secondary hypertriglyceridemia due to diabetes, renal disease, , alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-1 protease inhibitors, retinoic acid derivatives, interferons, or lasparaginase.
• On lomitapide or participating in clinical trial of volanesorsen and olezarsen
• On cyclosporine
• Having serum TSH outside of the normal range if on levothyroxine supplementation.
• Use of levothyroxine to suppress TSH in individuals with thyroid cancer.
• 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 or 168 g per week for men)
• Severe anemia (hematocrit < 24%)
• Illicit 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
• Previous history of renal calcium oxalate stones

• Minimum Eligible Age: 8 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 G Garg, MD

Role: PRINCIPAL_INVESTIGATOR

UT Southwestern Medical Center

Chandna Vasandani, Ph.D

Role: STUDY_DIRECTOR

UT Southwestern Medical Center

Locations

UT southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Abhimanyu G [agarg], MD

Role: CONTACT

abhimanyu.garg@utsouthwestern.edu

2146482895

Abhimanyu G [agarg]

Role: CONTACT

abhimanyu.garg@utsouthwestern.edu

2146482895

Facility Contacts

Abhimanyu G [agarg], MD

Role: primary

abhimanyu.garg@utsouthwestern.edu

214-648-2895

Chandna Vasandani, Ph.D

Role: backup

chandna.vasandani@utsouthwestern.edu

2146485074

Other Identifiers

STU-2019-0776

Identifier Type: -

Identifier Source: org_study_id