Cholesterol + Antioxidants for Smith-Lemli-Opitz Syndrome

Overseen By Ellen R Elias, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Colorado, Denver

Must be taking: Cholesterol, Antioxidants

Disqualifiers: No 7-dehydrocholesterol, Antioxidant allergy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1-2 years

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for Smith-Lemli-Opitz Syndrome (SLOS), a condition affecting cholesterol levels and causing developmental issues. Researchers are testing whether cholesterol supplements and antioxidants, such as Vitamin E, can improve health, particularly in vision and hearing. Participants will receive these treatments and undergo regular check-ups, including eye and hearing exams. This trial suits those with a confirmed SLOS diagnosis who can travel to Children's Hospital Colorado and have insurance for specific tests. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in SLOS treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that antioxidant vitamins, such as vitamin E, are generally safe even in high amounts. One study found that taking large doses of vitamin E results in few side effects. Antioxidants may also help address some issues caused by Smith-Lemli-Opitz Syndrome (SLOS).

Regarding cholesterol supplements, studies indicate they are used safely in people with SLOS, with patients closely monitored to catch any issues early. Another study found that the cholesterol-lowering drug simvastatin is also relatively safe for SLOS patients.

Overall, both antioxidants and cholesterol treatments appear well-tolerated. Patients receive careful monitoring to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using cholesterol and antioxidants for Smith-Lemli-Opitz Syndrome (SLOS) because this approach targets the unique biochemical imbalances in the condition. Unlike standard treatments that mainly focus on supplementing cholesterol, this method also aims to reduce harmful oxysterols with antioxidants, potentially improving outcomes in areas like vision and hearing. By measuring how antioxidants affect oxysterols and sensory functions, this treatment could pave the way for personalized dosing and identifying the most effective antioxidants for SLOS patients.

What evidence suggests that this trial's treatments could be effective for Smith-Lemli-Opitz Syndrome?

In this trial, participants with Smith-Lemli-Opitz Syndrome (SLOS) will receive treatments involving cholesterol supplementation and antioxidants, including vitamin E. Research has shown that cholesterol supplementation is a common treatment for SLOS and can lead to noticeable behavioral improvements. Studies also indicate that vitamin E helps protect cells by preventing harmful changes in 7-DHC, a substance that accumulates in people with SLOS. In some patients with SLOS already taking cholesterol, vitamin E showed positive effects over three years. Together, these treatments aim to address the chemical issues in SLOS, potentially leading to better health outcomes. ^{2 3 6 7 8}

Who Is on the Research Team?

Ellen R Elias, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

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

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

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Antioxidants
• Cholesterol

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Vitamin E for:

• General health and wellness
• Antioxidant supplementation

Approved in European Union as Vitamin E for:

• General health and wellness
• Antioxidant supplementation

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+

Published Research Related to This Trial

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]

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]

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 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 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3874268/

Antioxidant supplementation ameliorates molecular deficits ... In summary, we find that antioxidants, and specifically vitamin E supplementation, effectively inhibit the peroxidation of 7-DHC in SLOS human fibroblasts and ...

2. mdpi.com mdpi.com/2218-273X/11/8/1228

Biochemical and Clinical Effects of Vitamin E ... In a three-year prospective study, we investigated the effects of vitamin E supplementation in six SLOS patients already receiving dietary cholesterol ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01773278

Cholesterol and Antioxidant Treatment in Patients With ... Patients with biochemically confirmed SLOS are being treated with cholesterol supplementation and antioxidant medication. They are carefully monitored with ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S000632231300591X

Antioxidant Supplementation Ameliorates Molecular ... It was observed that vitamin E supplementation was effective to reduce cardiovascular events and diabetic nephropathy in individuals with Type 2 ...

5. biologicalpsychiatryjournal.com biologicalpsychiatryjournal.com/article/S0006-3223(13)00591-X/abstract

Antioxidant Supplementation Ameliorates Molecular ... Antioxidant Supplementation Ameliorates Molecular Deficits in Smith-Lemli-Opitz Syndrome ... SLOS model revealed that feeding a vitamin E enriched diet to ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8393612/

Biochemical and Clinical Effects of Vitamin E ... Smith-Lemli-Opitz syndrome (SLOS) is a severe monogenic disorder resulting in low cholesterol and high 7-dehydrocholesterol (7-DHC) levels.

7. gimjournal.org gimjournal.org/article/S1098-3600(25)00097-8/fulltext

Smith-Lemli-Opitz syndrome: Clinical, biochemical, and ... Animal studies indicate that antioxidants can reverse oxysterol-induced gene expression changes, leading to normalization of the lipid transcription profile. In ...

8. withpower.com withpower.com/trial/phase-3-syndrome-11-2008-e6d20

Cholesterol + Antioxidants for Smith-Lemli-Opitz Syndrome 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 ...