Cholesterol + Antioxidants for Smith-Lemli-Opitz Syndrome

Recruiting in Palo Alto (17 mi)

Overseen by Ellen R Elias, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Colorado, Denver

Must be taking: Cholesterol, Antioxidants

Disqualifiers: No 7-dehydrocholesterol, Antioxidant allergy

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial involves giving SLOS patients extra cholesterol and antioxidants to manage their condition. The treatment helps by providing necessary cholesterol and protecting against harmful substances. The goal is to improve health outcomes for these patients. Smith-Lemli-Opitz syndrome (SLOS) has been previously treated with cholesterol supplementation and statins to manage cholesterol synthesis defects.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Cholesterol + Antioxidants for Smith-Lemli-Opitz Syndrome?

Research shows that vitamin E, a key antioxidant, can protect LDL (a type of cholesterol) from oxidation, which is a process that can lead to heart disease. While this doesn't directly relate to Smith-Lemli-Opitz Syndrome, it suggests that antioxidants like vitamin E might help manage cholesterol-related issues. ^{1 2 3 4 5}

Is the combination of cholesterol and antioxidants, like vitamin E, safe for humans?

Vitamin E, a common antioxidant, is generally safe for humans even at high doses, with few side effects reported. Antioxidant vitamins, including vitamin E, are widely used and considered safe, although caution is advised for certain groups like pregnant women and those with liver or kidney issues. ^{3 6 7 8 9}

How is the treatment of Cholesterol + Antioxidants for Smith-Lemli-Opitz Syndrome different from other treatments?

This treatment is unique because it combines cholesterol supplementation with antioxidants like vitamin E, which may help protect against oxidative stress (damage caused by free radicals) and support cholesterol metabolism, unlike other treatments that might not address both aspects simultaneously. ^{1 3 9 10 11}

Research Team

Ellen R Elias, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

This trial is for patients with Smith-Lemli-Opitz Syndrome (SLOS), who have high levels of specific cholesterol byproducts and can visit Children's Hospital Colorado yearly. They must also have insurance that covers certain eye and ear tests. People allergic to antioxidants or without detectable cholesterol byproducts cannot join.

Inclusion Criteria

I have been diagnosed with Smith-Lemli-Opitz Syndrome.

Must be able to travel to Children's Hospital Colorado annually

Must have insurance coverage for ERG/ABR studies

Exclusion Criteria

You are allergic to antioxidant medication.

Your body does not have detectable levels of 7-dehydrocholesterol or 8-dehydrocholesterol.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients with SLOS are treated with cholesterol supplementation and antioxidant medication. Monitoring includes clinic visits, laboratory testing, and serial tests under anesthesia.

1-2 years

Annual visits for serial tests under anesthesia

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in ERG, blood oxysterol levels, and ABR testing.

12-24 months

Treatment Details

Interventions

• Antioxidants (Other)
• Cholesterol (Other)

Trial Overview The study is testing the effects of giving cholesterol and antioxidant supplements to SLOS patients. Their health is tracked through regular clinic visits, blood tests, vitamin level checks, and annual under-anesthesia exams including vision and hearing assessments.

Participant Groups

Group I: antioxidant effects on retinal function Experimental Treatment 2 Interventions

Patients with SLOS will be treated with both cholesterol supplementation and antioxidants. Retinal function will be followed by serial electroretinogram (ERG) testing and pigmentary retinopathy will be followed by Serial Ophthalmologic exams under anesthesia

Group II: antioxidant effects on hearing Experimental Treatment 2 Interventions

Patients with SLOS will be treated with cholesterol and antioxidant medication and their hearing will be followed by serial brainstem audiometry (ABR)

Group III: Antioxidant effect on Oxysterols Experimental Treatment 2 Interventions

Patients with SLOS will be treated with antioxidants and cholesterol. Blood oxysterol levels will be measured. Future focus will be on being able to use oxysterol levels to regulate antioxidant doses, and to determine which particular antioxidants might have the most benefit in lowering oxysterols

Antioxidants is already approved in Canada for the following indications:

Approved in Canada as Vitamin E for:

• General health and wellness
• Antioxidant supplementation

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Aviva Abosch

University of Colorado, Denver

Chief Medical Officer since 2019

MD

Uday B. Kompella

University of Colorado, Denver

Chief Executive Officer since 2015

PhD in Pharmaceutical Sciences

Findings from Research

In a study involving hypercholesterolemic patients on statin therapy, vitamin E supplementation significantly increased plasma alpha-tocopherol levels but did not lead to any meaningful changes in total or low-density lipoprotein (LDL) cholesterol levels.

While a small decrease in high-density lipoprotein (HDL) cholesterol was observed in the vitamin E group, it did not affect the overall cardiac risk ratio and was not linked to changes in key metabolic enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of vitamin E on cholesterol levels of hypercholesterolemic patients receiving statins. Leonard, SW., Joss, JD., Mustacich, DJ., et al.[2019]

In a 4-year study involving 15 patients with homozygous familial hypercholesterolemia, vitamin E therapy did not prevent the progression of atherosclerosis, as indicated by increasing carotid intima-media thickness.

In contrast, high-dose statin therapy led to a regression of atherosclerosis, demonstrating its efficacy in managing this condition compared to antioxidant therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of vitamin E compared with either simvastatin or atorvastatin in preventing the progression of atherosclerosis in homozygous familial hypercholesterolemia. Raal, FJ., Pilcher, GJ., Veller, MG., et al.[2019]

In a 3-month trial involving 15 hypercholesterolemic subjects, daily supplementation of 800 IU of vitamin E effectively normalized levels of lipid peroxidation products, indicating its potential role in reducing oxidative stress.

Despite the positive effects on lipid peroxidation, vitamin E supplementation did not lead to significant changes in serum cholesterol levels, suggesting that while it may help with oxidative damage, it does not directly impact cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship between serum lipid peroxidation products in hypercholesterolemic subjects and vitamin E status. Bierenbaum, ML., Reichstein, RP., Bhagavan, HN., et al.[2013]

Vitamin E supplementation significantly protects low density lipoprotein (LDL) from oxidation caused by copper and macrophages, extending the lag time before oxidation begins by 2.9 times.

Enriching LDL with vitamin E reduces its accumulation in macrophages and inhibits the formation of cholesteryl esters, suggesting that vitamin E can help prevent harmful oxidative processes in cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of supplementing with vitamin E on the uptake of low density lipoprotein and the stimulation of cholesteryl ester formation in macrophages. Suzukawa, M., Abbey, M., Clifton, P., et al.[2019]

In a study involving eight subjects, long-term supplementation with high doses of vitamin E significantly reduced the susceptibility of LDL to oxidation by 50%, indicating its potential protective role against atherosclerosis.

Conversely, while beta-carotene supplementation increased its levels in LDL, it did not affect LDL oxidation, suggesting that vitamin E is more effective than beta-carotene in protecting LDL from oxidative damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of dietary antioxidant combinations in humans. Protection of LDL by vitamin E but not by beta-carotene. Reaven, PD., Khouw, A., Beltz, WF., et al.[2019]

Oral intake of vitamin E is generally safe, with low toxicity and minimal side effects reported even at high doses of up to 3200 mg/d (3200 IU/d) in human studies.

Vitamin E supplementation has shown inconsistent effects on serum lipid and lipoprotein levels, but animal studies indicate it is not harmful in terms of mutagenicity, carcinogenicity, or teratogenicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of oral intake of vitamin E. Bendich, A., Machlin, LJ.[2018]

Vitamin E is a powerful antioxidant that protects against oxidative stress and may help reduce the risk of cardiovascular disease (CVD), supported by various studies including basic science, animal research, and clinical trials involving heart disease.

Clinical trials suggest that vitamin E supplementation (100 to 800 IU/d) is safe and may provide benefits not only for heart disease but also for other conditions, such as improving immune function and potentially reducing the risk of diseases like prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin E and heart disease: basic science to clinical intervention trials. Pryor, WA.[2019]

Antioxidant vitamins like vitamin A, beta-carotene, vitamin E, and ascorbic acid are widely consumed in the U.S., with about 40% of the population taking supplements, but their efficacy remains unproven and safety is questioned.

While vitamin A can cause toxicity at high doses (over 100,000 IU/d), and vitamin E and ascorbic acid have rare adverse effects at lower doses, caution is advised for certain groups, including women of childbearing age and individuals with liver or kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of antioxidant vitamins. Meyers, DG., Maloley, PA., Weeks, D.[2013]

In a study involving 30 hypercholesterolemic patients and 20 healthy subjects, atorvastatin significantly reduced oxidative stress markers (isoprostanes) within just 3 days, indicating an early antioxidant effect independent of cholesterol lowering.

Atorvastatin also increased plasma vitamin E levels by 42% after 30 days, suggesting that its antioxidant properties may enhance vitamin E circulation, alongside a notable reduction in cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic patients: effect on circulating vitamin E. Cangemi, R., Loffredo, L., Carnevale, R., et al.[2018]

The combination of 17beta-estradiol and vitamin E effectively protects LDL (low-density lipoprotein) from oxidation in postmenopausal women, which is important for cardiovascular health.

However, the study found that there was no additional benefit (synergism) from using both therapies together compared to administering either therapy alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of combined 17 beta-estradiol and vitamin E on low-density lipoprotein oxidation in postmenopausal women. Guetta, V., Panza, JA., Waclawiw, MA., et al.[2019]

In a study involving 20 healthy volunteers, it was found that even a low dose of 25 IU/d of vitamin E (D,L-alpha-tocopherol) significantly increased the resistance of LDL to oxidation, indicating its potential protective role against atherogenesis.

Higher doses of vitamin E (up to 800 IU/d) further enhanced LDL oxidation resistance, with plasma and LDL alpha-tocopherol levels increasing linearly, suggesting that higher supplementation may provide additional benefits in protecting against cardiovascular diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementation with low doses of vitamin E protects LDL from lipid peroxidation in men and women. Princen, HM., van Duyvenvoorde, W., Buytenhek, R., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Effects of vitamin E on cholesterol levels of hypercholesterolemic patients receiving statins. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy of vitamin E compared with either simvastatin or atorvastatin in preventing the progression of atherosclerosis in homozygous familial hypercholesterolemia. [2019]

3. Australia pubmed.ncbi.nlm.nih.gov

Relationship between serum lipid peroxidation products in hypercholesterolemic subjects and vitamin E status. [2013]

4. Ireland pubmed.ncbi.nlm.nih.gov

Effects of supplementing with vitamin E on the uptake of low density lipoprotein and the stimulation of cholesteryl ester formation in macrophages. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of dietary antioxidant combinations in humans. Protection of LDL by vitamin E but not by beta-carotene. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Safety of oral intake of vitamin E. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Vitamin E and heart disease: basic science to clinical intervention trials. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Safety of antioxidant vitamins. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic patients: effect on circulating vitamin E. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Effect of combined 17 beta-estradiol and vitamin E on low-density lipoprotein oxidation in postmenopausal women. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Supplementation with low doses of vitamin E protects LDL from lipid peroxidation in men and women. [2019]