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Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia

Primary Purpose

Type 1 Hyperlipoprotenemia

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Orlistat
Placebo
Sponsored by
University of Texas Southwestern Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Type 1 Hyperlipoprotenemia

Eligibility Criteria

8 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Type I hyperlipoproteinemia confirmed by bi-allelic disease-causing variants in any one of the T1HLP genes (LPL, APOC2, APOA5, LMF1, GPIHBP1, or GCKR). Fasting serum triglyceride levels of greater than 1000 mg/dL. Age 8-70 years Effective contraception for males and females of childbearing age. Off orlistat for a period of 2 months. Exclusion Criteria: Secondary hypertriglyceridemias due to diabetes, renal disease, hypothyroidism, alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-1 protease inhibitors, retinoic acid derivatives, interferons, or l-asparaginase. On lomitapide or participating in clinical trial of volanesorsen 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Orlistat Drug

    Placebo

    Arm Description

    Drug will be given orally.

    Placebo will be given orally.

    Outcomes

    Primary Outcome Measures

    Change in Triglycerides
    Change in fasting serum TG levels weeks compared to the baseline fasting serum TG levels .

    Secondary Outcome Measures

    Full Information

    First Posted
    April 1, 2023
    Last Updated
    October 11, 2023
    Sponsor
    University of Texas Southwestern Medical Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05816343
    Brief Title
    Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia
    Official Title
    Long Term Efficacy and Safety of Orlistat for Type 1 Hyperlipoproteinemia: a Randomized, Double-blind, Placebo-controlled Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 15, 2023 (Anticipated)
    Primary Completion Date
    April 15, 2025 (Anticipated)
    Study Completion Date
    July 30, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Texas Southwestern Medical Center

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Type 1 Hyperlipoprotenemia

    7. Study Design

    Primary Purpose
    Diagnostic
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Model Description
    A randomized, double-blind, placebo-controlled, parallel, study design will be employed for the first 24 weeks (Phase 1) followed by an open-labeled period of 24 weeks (Phase 2).
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    28 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Orlistat Drug
    Arm Type
    Active Comparator
    Arm Description
    Drug will be given orally.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo will be given orally.
    Intervention Type
    Drug
    Intervention Name(s)
    Orlistat
    Other Intervention Name(s)
    Alli
    Intervention Description
    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
    Intervention Name(s)
    Placebo
    Intervention Description
    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).
    Primary Outcome Measure Information:
    Title
    Change in Triglycerides
    Description
    Change in fasting serum TG levels weeks compared to the baseline fasting serum TG levels .
    Time Frame
    24 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    8 Years
    Maximum Age & Unit of Time
    70 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Type I hyperlipoproteinemia confirmed by bi-allelic disease-causing variants in any one of the T1HLP genes (LPL, APOC2, APOA5, LMF1, GPIHBP1, or GCKR). Fasting serum triglyceride levels of greater than 1000 mg/dL. Age 8-70 years Effective contraception for males and females of childbearing age. Off orlistat for a period of 2 months. Exclusion Criteria: Secondary hypertriglyceridemias due to diabetes, renal disease, hypothyroidism, alcoholism and drug therapy such as estrogens and estrogen analogues, steroids, HIV-1 protease inhibitors, retinoic acid derivatives, interferons, or l-asparaginase. On lomitapide or participating in clinical trial of volanesorsen 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Abhimanyu G [agarg], MD
    Phone
    2146482895
    Email
    abhimanyu.garg@utsouthwestern.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Abhimanyu G [agarg]
    Phone
    2146482895
    Email
    abhimanyu.garg@utsouthwestern.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Abhimanyu G Garg, MD
    Organizational Affiliation
    UT Southwestern Medical Center
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Chandna Vasandani
    Organizational Affiliation
    UT Southwestern Medical Center
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Undecided

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