Cholesterol + Antioxidants for Smith-Lemli-Opitz Syndrome
Recruiting in Palo Alto (17 mi)
Overseen byEllen 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.
12345Is 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.
36789How 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.
1391011Eligibility 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
+1 more
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: antioxidant effects on retinal functionExperimental Treatment2 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 hearingExperimental Treatment2 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 OxysterolsExperimental Treatment2 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Children's Hospital ColoradoAurora, CO
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Who Is Running the Clinical Trial?
University of Colorado, DenverLead Sponsor
References
Effects of vitamin E on cholesterol levels of hypercholesterolemic patients receiving statins. [2019]The effects of vitamin E supplementation on the cholesterol levels of hypercholesterolemic patients receiving statin therapy were studied.
Efficacy of vitamin E compared with either simvastatin or atorvastatin in preventing the progression of atherosclerosis in homozygous familial hypercholesterolemia. [2019]Over a 4-year period, antioxidant therapy (vitamin E) was compared with high-dose statin therapy in 15 patients with homozygous familial hypercholesterolemia. Carotid intima-media thickness, used as an in vivo assessment of atherosclerosis, progressed rapidly during the period of vitamin E therapy but regressed on statin therapy.
Relationship between serum lipid peroxidation products in hypercholesterolemic subjects and vitamin E status. [2013]The relationship of serum lipid peroxidation products in hypercholesterolemic subjects to their vitamin E intake was examined in 15 such subjects with no other associated significant disease process in a 3 month trial with vitamin E supplementation. These patients with elevated serum cholesterol levels also have elevated thiobarbituric acid reactive substances (TBARS) and lipid oxidation products (LOPS). Vitamin E supplementation of 800 IU daily normalized the lipid peroxidation products but did not significantly change serum lipids.
Effects of supplementing with vitamin E on the uptake of low density lipoprotein and the stimulation of cholesteryl ester formation in macrophages. [2019]Vitamin E supplementation has been reported to protect low density lipoprotein (LDL) from copper-induced oxidation and macrophage-mediated oxidation. We investigated the effect of in vitro vitamin E enrichment of LDL on the accumulation of [3H]cholesteryl ester (CE)-LDL and stimulation of cholesteryl ester formation in J774 macrophages. Vitamin E supplementation prolonged lag time (2.9-fold) before the initiation of copper-induced LDL oxidation. LDL, preincubated with 5 microM copper or with macrophages in Ham's F10 medium, accumulated in macrophages much more than did native LDL. However, following vitamin E enrichment, LDL accumulation was significantly reduced following oxidative stress. Vitamin E-enriched LDL also reduced the stimulation of cholesteryl ester formation in macrophages. Moreover, vitamin E enrichment of macrophages reduced the ability of the cells to oxidize LDL. The present results indicate that vitamin E supplementation protects LDL against copper-induced and macrophage-mediated oxidation, inhibits oxidation-dependent accumulation of LDL in macrophages, and prevents stimulation of cholesteryl ester formation in macrophages. Additionally we have provided evidence that intra-cellular enrichment with vitamin E prevents oxidative modification of LDL by macrophages.
Effect of dietary antioxidant combinations in humans. Protection of LDL by vitamin E but not by beta-carotene. [2019]Experimental and epidemiological evidence supports the hypothesis that oxidation of low density lipoprotein (LDL) appears to be important in mediating the atherogenicity of LDL. To test this hypothesis in humans, it will be necessary to perform intervention studies in large populations. We performed two studies to assess the effectiveness of supplementation with beta-carotene and vitamin E, used alone and in combination with each other, and with vitamin C, to protect LDL from oxidation. In phase 1, after a placebo period, eight subjects were given beta-carotene (60 mg/day) for 3 months, then beta-carotene plus vitamin E (1,600 mg/day) for another 3 months, and then beta-carotene plus vitamin E plus vitamin C (2 g/day) for 3 months. During phase 2, beta-carotene and vitamin C were discontinued, and subjects took only vitamin E for 5 months. During each period, LDL samples were isolated, and measurements of susceptibility to oxidation were performed. beta-Carotene levels in LDL increased nearly 20-fold, but LDL susceptibility to oxidation did not change. Addition of vitamin E increased LDL vitamin E levels nearly 2.5-fold, and this decreased LDL oxidation 30-40%. During the vitamin C supplementation period, plasma levels of beta-carotene and vitamin E rose, but only beta-carotene increased in LDL. However, the susceptibility of LDL to oxidation in this period was not decreased further. During phase 2, when subjects took only vitamin E, LDL susceptibility to oxidation was decreased by 50% as measured by thiobarbituric acid-reactive substances, conjugated dienes, and lipid peroxide formation as well as by macrophage degradation. Thus, long-term supplementation with large doses of vitamin E alone, but not beta-carotene, conferred increased protection to LDL in in vitro assays of oxidation. These data should be useful in planning therapeutic strategies to test the antioxidant hypothesis in humans.
Safety of oral intake of vitamin E. [2018]A review of the literature concerning the safety of oral intake of vitamin E indicated that the toxicity of vitamin E is low. Vitamin E supplementation has resulted in inconsistent effects in serum lipid and lipoprotein levels. Animal studies showed that vitamin E is not mutagenic, carcinogenic, or teratogenic. In human studies with double-blind protocols and in large population studies, oral vitamin E supplementation resulted in few side effects even at doses as high as 3200 mg/d (3200 IU/d).
Vitamin E and heart disease: basic science to clinical intervention trials. [2019]A review is presented of studies on the effects of vitamin E on heart disease, studies encompassing basic science, animal studies, epidemiological and observational studies, and four intervention trials. The in vitro, cellular, and animal studies, which are impressive both in quantity and quality, leave no doubt that vitamin E, the most important fat-soluble antioxidant, protects animals against a variety of types of oxidative stress. The hypothesis that links vitamin E to the prevention of cardiovascular disease (CVD) postulates that the oxidation of unsaturated lipids in the low-density lipoprotein (LDL) particle initiates a complex sequence of events that leads to the development of atherosclerotic plaque. This hypothesis is supported by numerous studies in vitro, in animals, and in humans. There is some evidence that the ex vivo oxidizability of a subject's LDL is predictive of future heart events. This background in basic science and observational studies, coupled with the safety of vitamin E, led to the initiation of clinical intervention trials. The three trials that have been reported in detail are, on balance, supportive of the proposal that supplemental vitamin E can reduce the risk for heart disease, and the fourth trial, which has just been reported, showed small, but not statistically significant, benefits. Subgroup analyses of cohorts from the older three trials, as well as evidence from smaller trials, indicate that vitamin E provides protection against a number of medical conditions, including some that are indicative of atherosclerosis (such as intermittent claudication). Vitamin E supplementation also produces an improvement in the immune system and protection against diseases other than cardiovascular disease (such as prostate cancer). Vitamin E at the supplemental levels being used in the current trials, 100 to 800 IU/d, is safe, and there is little likelihood that increased risk will be found for those taking supplements. About one half of American cardiologists take supplemental vitamin E, about the same number as take aspirin. In fact, one study suggests that aspirin plus vitamin E is more effective than aspirin alone. There are a substantial number of trials involving vitamin E that are in progress. However, it is possible, or even likely, that each condition for which vitamin E provides benefit will have a unique dose-effect curve. Furthermore, different antioxidants appear to act synergistically, so supplementation with vitamin E might be more effective if combined with other micronutrients. It will be extremely difficult to do trials that adequately probe the dose-effect curve for vitamin E for each condition that it might affect, or to do studies of all the possible combinations of other micronutrients that might act with vitamin E to improve its effectiveness. Therefore, the scientific community must recognize that there never will be a time when the science is "complete." At some point, the weight of the scientific evidence must be judged adequate; although some may regard it as early to that judgement now, clearly we are very close. In view of the very low risk of reasonable supplementation with vitamin E, and the difficulty in obtaining more than about 30 IU/day from a balanced diet, some supplementation appears prudent now.
Safety of antioxidant vitamins. [2013]As a result of the many scientific and popular press reports of the benefits of antioxidant vitamins (vitamin A, beta-carotene, vitamin E, and ascorbic acid), it is estimated that 40% of the US population is consuming vitamin supplements. The efficacy of these supplements is not yet proved, and some have questioned their safety. Approximately 10 to 15 cases of vitamin A toxic reactions are reported per year in the United States, usually at doses greater than 100,000 IU/d. No adverse effects have been reported for beta-carotene. The frequency of vitamin E toxic reactions is not well delineated, but case reports are few at dosages less than 3200 mg/d. Ascorbic acid toxic reactions are rare at dosages less than 4 g/d. Despite a lack of clinical trial data, it seems that antioxidant vitamins are safe, although prudence might dictate their avoidance by women of childbearing potential, persons with liver disease or renal dysfunction, and those taking certain medications or undergoing specific laboratory tests.
Early decrease of oxidative stress by atorvastatin in hypercholesterolaemic patients: effect on circulating vitamin E. [2018]Statins inhibit oxidative stress, but the interplay between cholesterol lowering and antioxidant vitamins is still unclear. Aims of the study were to assess if statins inhibit oxidative stress independently from cholesterol lowering, to assess the behaviour of vitamin E simultaneously with the changes of oxidative stress, to determine in vitro if atorvastatin was able to directly influence platelet-mediated LDL oxidation and vitamin E consumption.
Effect of combined 17 beta-estradiol and vitamin E on low-density lipoprotein oxidation in postmenopausal women. [2019]In conclusion, combined administration of 17beta-estradiol and vitamin E protects LDL in postmenopausal women from oxidation with no synergism noted compared with either therapy given alone.
Supplementation with low doses of vitamin E protects LDL from lipid peroxidation in men and women. [2019]There is accumulating evidence that oxidative modification of LDL is an important step in the process of atherogenesis and that antioxidants may protect LDL from oxidation. We and others have previously shown that ingestion of pharmacological doses of the antioxidant D,L-alpha-tocopherol (vitamin E), far above the recommended daily intake (ie, 12 to 15 IU/d for adults), increases the oxidation resistance of LDL. In this study, we ascertained the minimal supplementary dose of vitamin E necessary to protect LDL against oxidation in vitro. Twenty healthy volunteers (10 men and 10 women, aged 21 to 31 years) ingested consecutively 25, 50, 100, 200, 400, and 800 IU/d, D,L-alpha-tocopherol acetate during six 2-week periods. No changes were observed in LDL triglyceride content, fatty acid composition of LDL, or LDL size during the intervention. Concentrations of alpha-tocopherol in plasma and LDL were both 1.2 times the baseline values after the first period (25 IU/d) and 2.6 and 2.2 times, respectively, after the last period (800 IU/d). There was a linear increase in LDL alpha-tocopherol levels up to an intake of 800 IU/d (r = .79, P