Orlistat for High Cholesterol

Overseen By Abhimanyu G [agarg]

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: Estrogens, Steroids, Cyclosporine, others

Disqualifiers: Diabetes, Renal disease, Alcoholism, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether orlistat, a medication typically used for weight loss, can reduce high blood fat levels in individuals with Type I hyperlipoproteinemia (T1HLP). T1HLP is a rare condition that causes extremely high triglycerides in the blood, often leading to health issues because standard treatments are ineffective. Participants will receive either orlistat or a placebo (a pill with no active ingredients) to compare outcomes. Eligible participants must have confirmed T1HLP and fasting triglyceride levels of at least 750 mg/dL. As a Phase 2 trial, this research aims to assess the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that orlistat is likely to be safe for humans?

Research shows that orlistat is generally safe for most people. This medication aids weight loss and can also lower cholesterol levels. Most individuals taking orlistat may experience mild side effects such as stomach cramps, gas, and changes in bowel habits, but these are usually manageable.

Rare reports of serious liver problems have occurred in people using orlistat, though these cases are uncommon. The FDA reviewed orlistat's safety in 2010, ensuring close monitoring. Since orlistat is approved for weight loss, extensive information about its safety helps doctors and researchers understand its effects on the body.

Overall, orlistat has been well-studied, and evidence suggests it is safe for most people. However, as with any medication, discussing concerns with a doctor is important, especially if other health issues are present. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for T1HLP?

Unlike the standard treatments for high cholesterol, which often include statins like atorvastatin or simvastatin, orlistat offers a unique approach by targeting fat absorption in the digestive system. While most cholesterol-lowering drugs work by affecting liver enzymes or cholesterol production, orlistat blocks the absorption of dietary fats, which can indirectly help reduce cholesterol levels. This different mechanism of action, which involves the digestive tract rather than the circulatory system, makes orlistat a promising option for those who might experience side effects from traditional cholesterol medications. Researchers are excited about orlistat because it provides an alternative pathway to managing cholesterol, potentially benefiting patients who struggle with existing treatments.

What evidence suggests that orlistat might be an effective treatment for T1HLP?

Research shows that orlistat, which participants in this trial may receive, effectively lowers cholesterol levels. Studies have found that orlistat reduces total cholesterol and "bad" cholesterol (low-density lipoprotein or LDL cholesterol), even without weight loss. One study demonstrated that people taking orlistat significantly improved their cholesterol levels compared to those taking a placebo. This suggests that orlistat may help manage high blood fat levels by lowering cholesterol, which could benefit people with Type I hyperlipoproteinemia (T1HLP). ^{2 4 5 6 7}

Who Is on the Research Team?

Abhimanyu Garg

Principal Investigator

UT Southwestern Medical Center

Chandna Vasandani, Ph.D

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

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

I have not taken orlistat for at least 2 months.

I have a genetic form of high cholesterol due to specific gene mutations.

I am between 8 and 70 years old.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Orlistat
• Placebo

Trial Overview The 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.

How Is the Trial Designed?

Group I: Orlistat Drug Active Control 1 Intervention

Drug will be given orally.

Group II: Placebo Placebo Group 1 Intervention

Placebo will be given orally.

Orlistat is already approved in European Union, United States 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

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Published Research Related to This Trial

Orlistat, a lipase inhibitor, effectively reduces dietary fat absorption by about 30%, and when combined with a low-calorie, low-fat diet, it nearly doubles the success rate of obese individuals losing at least 10% of their initial body weight over two years.

In addition to weight loss, Orlistat also helps lower serum cholesterol levels by 6-10%, although it may cause intestinal side effects that typically lessen over time and with reduced fat intake.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacy-clinics medication of the month. Orlistate (xenical)]. Scheen, AJ., Ernest, P., Letiexhe, MR.[2018]

Orlistat, a pancreatic lipase inhibitor, significantly aids in weight loss for obese patients on a hypocaloric diet, with participants losing an average of 5% of their body weight compared to 3.5% for those on placebo over 12 weeks.

In long-term studies of up to 2 years, orlistat continued to show greater weight loss compared to placebo, with more patients achieving over 5% or 10% weight loss, indicating its sustained efficacy in managing obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Orlistat. McNeely, W., Benfield, P.[2018]

Current lipid-lowering therapies are effective and well-tolerated, but research is ongoing to find even better treatments, including new inhibitors and combination therapies.

Orlistat, a new antiobesity drug, has been shown to positively impact blood lipid profiles, and there is growing interest in improving HDL cholesterol levels through niacin and other enzyme inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipid-altering drugs in development. Bays, HE., Dujovne, CA.[2018]

In a study of 28 participants (13 obese and 15 non-obese), treatment with orlistat for 16 weeks led to significant reductions in BMI, blood pressure, insulin levels, and cholesterol levels in obese subjects, indicating its efficacy in promoting weight loss and improving metabolic health.

Orlistat treatment also resulted in increased levels of folic acid and vitamin B12, suggesting potential nutritional implications, while the relationship between leptin and NPY levels in obese patients remained unclear despite significant changes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of orlistat therapy on carbohydrate, lipid, vitamin and hormone plasma levels in obese subjects]. Czerwieńska, B., Kokot, F., Franek, E., et al.[2018]

Fibrates and niacin are effective in reducing small, dense low density lipoprotein (sdLDL) particles and shifting LDL size towards larger, healthier particles in obese patients with mixed dyslipidaemia.

Ezetimibe primarily decreases larger LDL subclasses and has a modest effect on sdLDL, while orlistat and rimonabant can reduce sdLDL-C levels and increase LDL particle size, suggesting a combination of these treatments may enhance LDL profile in overweight/obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of non-statin lipid lowering and anti-obesity drugs on LDL subfractions in patients with mixed dyslipidaemia. Florentin, M., Tselepis, AD., Elisaf, MS., et al.[2019]

Severe hypertriglyceridemia is linked to a higher risk of cardiovascular disease and pancreatitis, necessitating prompt hospitalization and treatment with hypolipidemic drugs, insulin/dextrose infusion, or therapeutic apheresis for affected patients.

Fibrates are the first-line treatment for severe hypertriglyceridemia, but often a combination of medications, including omega-3 fatty acids, niacin, and high-dose statins, is required to effectively manage triglyceride levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations for severe hypertriglyceridemia treatment, are there new strategies? Filippatos, TD., Elisaf, MS.[2019]

A case study of a nonobese Asian Indian man with severe hypertriglyceridemia showed that the combination of gemfibrozil and orlistat significantly reduced triglyceride levels from 766 mg/dL to as low as 224 mg/dL, demonstrating the efficacy of this combination therapy.

Monotherapy with either gemfibrozil or orlistat alone was ineffective, highlighting the need for further research into the mechanisms behind their synergistic effect in treating combined hyperlipidemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of gemfibrozil and orlistat for treatment of combined hyperlipidemia with predominant hypertriglyceridemia. Tolentino, MC., Ferenczi, A., Ronen, L., et al.[2021]

Raising high-density lipoprotein cholesterol (HDLC) in patients with low levels is considered in high-risk individuals, such as those with established heart disease or diabetes, but there is still uncertainty about the benefits of HDL-raising therapies due to a lack of event-based trials.

In high-risk patients, statins are typically used to lower low-density lipoprotein cholesterol (LDLC), and additional medications like niacin or fibrates may be added to effectively raise HDLC levels, although specific HDLC targets are not formally established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current Drug Options for Raising HDL Cholesterol. Dunbar, RL., Rader, DJ.[2020]

Orlistat is effective for weight reduction and maintenance, and it positively impacts cardiovascular risk factors associated with obesity, including lowering serum insulin levels and reducing the incidence of type 2 diabetes in at-risk patients.

In addition to weight loss, orlistat helps lower total and LDL cholesterol levels, improves triglyceride levels after meals, and has beneficial effects on inflammatory markers, indicating its multifaceted role in managing obesity-related health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of orlistat on metabolic parameters and other cardiovascular risk factors. Kiortsis, DN., Filippatos, TD., Elisaf, MS.[2020]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15153170/

Cholesterol lowering effect of dietary weight loss and ... Results: Weight loss in the orlistat group was 7.4 kg vs. 4.9 kg with placebo. Total and low-density lipoprotein cholesterol decreased by 25-30 mg/dL vs. 10-15 ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0011393X02800662

Effects of orlistat, simvastatin, and ... The combination treatment showed significantly greater reductions in serum TC and LDL-C levels, BMI, WCR, and BWL than with either orlistat or simvastatin alone ...

3. frontiersin.org frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.824269/full

The Effect of Orlistat on Sterol Metabolism in Obese Patients Orlistat has been shown to reduce serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels independent of weight loss (6, 8, 9). In line ...

4. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT00152360

The Effect of Xenical on Weight and Risk Factors | ... Studies of up to two years duration have demonstrated that those taking Xenical plus diet lost significantly more weight than those taking ...

5. europeanreview.org europeanreview.org/wp/wp-content/uploads/8326-8332-1.pdf

Significance of Orlistat in management of dyslipidemia, ... RESULTS: The study found that the Orlistat group has significant improvement (p<0.05) more improvement in LDL cholesterol, HDL cho- lesterol, Total cholesterol, ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK542202/

Orlistat - StatPearls - NCBI Bookshelf - NIH [1] The mean weight loss in patients by the end of 6 months of orlistat use is approximately 5.6 kg, whereas those in the placebo group show a ...

7. mayoclinic.org mayoclinic.org/healthy-lifestyle/weight-loss/in-depth/alli/art-20047908

Alli weight-loss pill: Does it work? Are there concerns about orlistat? The FDA published a safety review of orlistat in 2010 because of rare reports of serious liver injury in people using it.