Orlistat for High Cholesterol
Recruiting in Palo Alto (17 mi)
Age: Any Age
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Texas Southwestern Medical Center
Must not be taking: Estrogens, Steroids, Cyclosporine, others
Disqualifiers: Diabetes, Renal disease, Alcoholism, others
Prior Safety Data
Approved in 5 Jurisdictions
Trial Summary
What is the purpose of this trial?
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.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop all current medications, but you cannot participate if you are on certain drugs like lomitapide, anti-coagulants, digoxin, or anti-arrhythmics. You also need to be off orlistat for 2 months before joining.
What evidence supports the effectiveness of the drug Orlistat for high cholesterol?
How does the drug Orlistat differ from other treatments for high cholesterol?
Orlistat is unique because it works by blocking the absorption of dietary fat in the intestines, which not only helps with weight loss but also reduces cholesterol levels. Unlike other cholesterol-lowering drugs that work directly in the bloodstream, Orlistat acts in the digestive system and is taken with meals.26789
Eligibility Criteria
This trial is for people aged 8-70 with a rare condition called Type I hyperlipoproteinemia, confirmed by specific genetic variants. They must have very high blood fat levels (≥1000 mg/dL) and not have taken orlistat recently. Both men and women of childbearing age should use effective contraception.Inclusion Criteria
Fasting serum triglyceride levels of greater than 1000 mg/dL.
Effective contraception for males and females of childbearing age.
I have not taken orlistat for at least 2 months.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
8 weeks
Outpatient visits
Baseline
Participants consume an extremely low fat diet (≤15% of total energy from fat) and undergo baseline assessments
8 weeks
Outpatient visits
Treatment
Participants are randomly assigned to receive either Orlistat or placebo for 24 weeks
24 weeks
Outpatient visits with blood lipids and chemistry panel analysis
Open-label Extension
All participants receive Orlistat for an additional 24 weeks
24 weeks
Outpatient visits with blood lipids and chemistry panel analysis
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Orlistat (Lipase Inhibitor)
- Placebo (Other)
Trial OverviewThe trial is testing the long-term effectiveness and safety of a drug called orlistat in reducing extremely high triglyceride (blood fat) levels in patients with Type I hyperlipoproteinemia, compared to a placebo.
Participant Groups
2Treatment groups
Active Control
Placebo Group
Group I: Orlistat DrugActive Control1 Intervention
Drug will be given orally.
Group II: PlaceboPlacebo Group1 Intervention
Placebo will be given orally.
Orlistat is already approved in European Union, United States, United States, Australia for the following indications:
🇪🇺 Approved in European Union as Xenical for:
- Obesity management
🇺🇸 Approved in United States as Xenical for:
- Obesity management in patients with BMI ≥ 30 kg/m² or BMI ≥ 27 kg/m² with other risk factors
🇺🇸 Approved in United States as Alli for:
- Weight loss in overweight adults 18 years and older when used along with a reduced-calorie and low-fat diet
🇦🇺 Approved in Australia as Xenical for:
- Obesity management
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UT southwestern Medical CenterDallas, TX
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Who Is Running the Clinical Trial?
University of Texas Southwestern Medical CenterLead Sponsor
References
Lipid-altering drugs in development. [2018]Although currently available lipid lowering therapies are effective and well tolerated, the search continues for additional treatments with even better efficacy and tolerability profiles. As well as refinements to existing strategies (new HMG-CoA reductase inhibitors, fibrates and combination therapies) new avenues are being explored. These include inhibitors of enzymes other than HMG-CoA reductase involved in cholesterol regulation and drugs which affect absorption of lipids from the gastrointestinal tract. In the case of the latter, it has been shown that the new antiobesity treatment orlistat can favourably affect the blood lipid profile. In line with an increasing emphasis on improving high density lipoprotein-cholesterol (HDL-C) levels, the potential therapeutic roles of niacin and drugs which inhibit enzymes involved in the metabolism of HDL-C are also being researched.
Effect of non-statin lipid lowering and anti-obesity drugs on LDL subfractions in patients with mixed dyslipidaemia. [2019]Small, dense low density lipoprotein (sdLDL) particles are considered an emerging cardiovascular risk factor. Obese patients with mixed dyslipidaemia frequently have elevated sdLDL cholesterol (sdLDL-C) levels. Therefore, agents that favourably modulate the LDL phenotype may be of clinical value in these patients. We review the efficacy of anti-obesity and lipid lowering drugs other than statins on LDL subfractions in patients with mixed dyslipidaemia primarily focusing on those who are overweight/obese. The literature search was based on PubMed listings up to 26 November 2009. In most studies ezetimibe decreases the large and medium LDL subclasses and, to a lesser extent, the sdLDL particles, while it does not substantially influence LDL size. Fibrates and niacin reduce sdLDL particles and shift LDL size towards large, buoyant LDL particles. More studies are needed to elucidate the effects of fish oils and resins on LDL phenotype. Orlistat and rimonabant have been associated with reductions in sdLDL-C levels along with an increase in LDL particle size. We did not find any literature describing the effect of sibutramine on sdLDL profile. Treatment with fibrates and niacin seems to be beneficial in patients with mixed dyslipidaemia. The addition of orlistat may further improve LDL phenotype in overweight/obese patients.
Recommendations for severe hypertriglyceridemia treatment, are there new strategies? [2019]This review considers drug combinations and newer treatment strategies for patients with severe hypertriglyceridemia. Hypertriglyceridemia is associated with an atherogenic metabolic profile and in most studies with increased cardiovascular disease risk. Patients with severe hypertriglyceridemia also have increased incidence of pancreatitis. All types of severe hypertriglyceridemia are associated with a reduction in lipoprotein lipase activity. Patients with severe hypertriglyceridemia and abdominal pain or pancreatitis should be hospitalized and treated with hypolipidemic drugs and, if needed, with insulin/dextrose infusion or therapeutic apheresis. Fibrates are the first-line treatment in patients with severe hypertriglyceridemia. Omega-3 fatty acids and niacin are very useful drugs for patients with hypertriglyceridemia. Statins in high doses exhibit a significant hypotriglyceridemic activity. Drugs that interfere with chylomicron production such as orlistat are also useful for hypertriglyceridemic patients. In most patients with severe hypertriglyceridemia drug combinations are needed to maintain an acceptable triglyceride concentration. Gene therapy is under development for patients with known genetic abnormalities of triglyceride metabolism. Clinicians should be vigilant for the recognition and prompt treatment of patients with severe hypertriglyceridemia aimed to avoid the serious complication of pancreatitis and to reduce their cardiovascular risk.
Combination of gemfibrozil and orlistat for treatment of combined hyperlipidemia with predominant hypertriglyceridemia. [2021]To present a case of combined hyperlipidemia with predominant hypertriglyceridemia unresponsive to conventional diet and single-agent drug therapy but successfully treated with a combination of gemfibrozil and orlistat.
Current Drug Options for Raising HDL Cholesterol. [2020]Although circumstantial evidence supports raising high-density lipoprotein cholesterol (HDLC) in patients with low levels of HDLC, the scarcity of event-based trials has led to uncertainty with regard to the benefit of high-density lipoprotein (HDL)-raising therapy. Based on the National Cholesterol Education Program guidelines, therapy for dyslipidemia is focused initially on targeting low-density lipoprotein cholesterol (LDLC), and in patients with hypertriglyceridemia, secondarily on targeting non-HDLC. When HDLC remains low, the decision to target HDLC depends on the assessment of risk of cardiovascular events. We often consider drug therapy specifically to raise HDLC in high-risk patients, such as those with established atherosclerotic vascular disease, type 2 diabetes, or a Framingham risk score of 20% or above. The majority of high-risk patients require drug therapy, usually a statin, to achieve aggressive LDLC and non-HDLC goals, and thus many patients with low HDLC are candidates for statin therapy. However, a second drug is often required to achieve substantial HDL raising. Although no formal goals for HDLC exist, reasonable goals are HDLC greater than 40 mg/dL in men and greater than 50 mg/dL in women. We often add either niacin or a fibrate to a statin in high-risk patients with low HDLC levels. Targeting HDLC with pharmacologic therapy is a more difficult decision in moderate-risk patients, in whom therapy must be highly individualized.
[Pharmacy-clinics medication of the month. Orlistate (xenical)]. [2018]Orlistat (tetrahydrolipstatin), launched by Roche under the trade name Xenical, is a selective inhibitor of pancreatic and gastro-intestinal lipases. It reduces the digestion of dietary fat and its resorption through digestive mucosa by around 30%. It is indicated, at a dose of 3 x 120 mg/day (one dose with each meal) and together with a moderately low-calorie and low-fat diet, for the treatment of obesity. It has been shown, in placebo-controlled two-year trials, to almost double the number of obese subjects who succeed in loosing at least 10% of initial body weight. Independently, it contributes to decrease serum cholesterol levels by 6-10%. Because of its mechanism of action, this drug can induce intestinal side-effects which tend to decrease with time and with the reduction of fat intake, thus improving diet compliance.
Orlistat. [2018]Orlistat (tetrahydrolipstatin) is an inhibitor of pancreatic and other lipases. As a pancreatic lipase inhibitor, it acts in the gastrointestinal lumen and is indicated for use in obesity. Serum total cholesterol and low density lipoprotein-cholesterol levels were reduced in obese, but otherwise healthy, patients during 5% or > 10% of their initial bodyweight in 1- and 2-year studies.
[Effect of orlistat therapy on carbohydrate, lipid, vitamin and hormone plasma levels in obese subjects]. [2018]Orlistat is an inhibitor of lipase which splits triglycerides into free fatty acides and glycerol. This drug, by inhibiting hydrolysis of triglycerides, is the cause of significant loss of fat in the faeces. 13 obese and 15 nonobese subjects were examined. Obese subjects received orlistat (Xenical, F. Hoffmann La Roche Ltd, Switzerland) 3 x 120 mg/d. Treatment with orlistat for 16 weeks was followed by a significant fall of BMI and MAP, insulinemia, insulin/glucose ratio, leptinemia, serum total cholesterol, triglycerides, HDL-cholesterol and 25-OH-D concentration respectively. Orlistat did not influence significantly serum LDL-cholesterol concentration but unexpectedly increased plasma levels of folic acid, vitamin B12 and NPY.
The effects of orlistat on metabolic parameters and other cardiovascular risk factors. [2020]Orlistat is an antiobesity drug with a well documented efficacy in weight reduction and weight maintenance. Weight reduction with orlistat has been associated with a favourable effect on obesity-related cardiovascular risk factors. Orlistat treatment is associated with a reduction in serum insulin levels. Moreover, orlistat reduces the incidence of type 2 diabetes in patients with impaired glucose tolerance and lowers the required dose of metformin, sulfonylureas and insulin in patients with type 2 diabetes. Furthermore, orlistat can reduce total and low density lipoprotein (LDL) cholesterol levels and improve postprandial triglyceridemia, as well as the low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio (LDL/HDL ratio). Moreover, orlistat appears to have a favourable effect on some inflammatory markers, such as TNF-alpha and interleukin-6 and has a time-depended effect on some haemostatic factors.