Statins for High Cholesterol in Children

Overseen By Jonathan B Wagner, DO

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Mercy Hospital Kansas City

Must be taking: Rosuvastatin

Must not be taking: OATP1B1 inducers/inhibitors

Disqualifiers: Pregnancy, Cardiovascular defects, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2 years

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how rosuvastatin, a statin used to lower cholesterol, affects liver function in children and teens with high cholesterol. Researchers aim to understand how the liver processes the medication in both overweight and non-overweight participants. The trial involves taking the medication and may include MRI scans to assess liver fat. Children and teens aged 8-21 with high LDL cholesterol and the SLCO1B1 c.521TT genotype might be suitable candidates, especially if they are not currently taking other cholesterol medications. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

If you are currently taking statins, you will need to stop them for at least 4 weeks before starting the trial and throughout its duration. The protocol does not specify about other medications, but if they interact with statins, you may need to stop them as well.

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

Research has shown that rosuvastatin, the treatment under study in this trial, is generally safe for children aged 8 and older. Studies have found that rosuvastatin does not harm growth or development in children with familial hypercholesterolemia, a genetic condition causing high cholesterol. The FDA has approved rosuvastatin for use in children 8 years and older to help manage high cholesterol. While side effects can occur, they are usually mild and may include muscle pain or digestive issues. Gathering more data remains important, highlighting the value of studies like this. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Rosuvastatin is unique because it targets high cholesterol in children by using a statin specifically designed to lower LDL cholesterol levels. Most cholesterol treatments focus on managing symptoms in adults, but Rosuvastatin is tailored for younger patients. Researchers are excited about its potential to effectively reduce cholesterol levels in children, which could prevent future heart-related issues. Unlike typical lifestyle changes or dietary supplements, Rosuvastatin works by directly inhibiting the enzyme responsible for cholesterol production, making it a promising option for early intervention.

What evidence suggests that rosuvastatin might be an effective treatment for high cholesterol in children?

Research has shown that rosuvastatin, which participants in this trial may receive, can effectively lower LDL cholesterol, often called "bad cholesterol," in children. In studies, daily rosuvastatin reduced LDL levels by 38% to 50%, depending on the dose. These results remained consistent across different trials, demonstrating the drug's ability to safely lower cholesterol levels. For children with familial hypercholesterolemia, a genetic condition that causes high cholesterol, rosuvastatin helped many achieve healthier cholesterol levels. Although not every child reached the target LDL level, the reduction was still significant and beneficial for heart health. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for obese and non-obese children and adolescents aged 8-21 with high LDL cholesterol levels who have a specific genotype (SLCO1B1 c.521TT). They must not be on statin therapy, can't be pregnant, should not have significant heart defects or unsafe metal implants for MRI, and must be able to swallow tablets.

Inclusion Criteria

LDL cholesterol >130mg/dl (>95% percentile)

I am between 8 and 21 years old.

I have the SLCO1B1 c.521TT genotype.

Exclusion Criteria

I cannot swallow pills.

Pregnancy

Non-fasting

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline Mevalonate and MRI Imaging to assess liver adiposity

1-2 weeks

Treatment

Participants receive rosuvastatin to evaluate the effect of liver fat percentage on statin disposition and response

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Rosuvastatin

Trial Overview The study tests the effects of Rosuvastatin (10mg) on liver fat in kids with high cholesterol. It's an open-label trial meaning everyone knows what treatment they're getting. The focus is on how body fat influences the drug's transport and effectiveness in the liver.

How Is the Trial Designed?

Group I: Mevalonate Change After Rosuvastatin Experimental Treatment 1 Intervention

Group II: Baseline Mevalonate and MRI Imaging Active Control 1 Intervention

Rosuvastatin is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Crestor for:

• High cholesterol
• Hyperlipoproteinemia
• Prevention of cardiovascular disease

Approved in European Union as Crestor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Canada as Crestor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Prevention of cardiovascular disease

Approved in Japan as Crestor for:

• Hypercholesterolemia
• Familial hypercholesterolemia

Who Is Running the Clinical Trial?

Children's Mercy Hospital Kansas City

Lead Sponsor

Trials

261

Recruited

941,000+

Published Research Related to This Trial

In the JUPITER trial, rosuvastatin significantly reduced the occurrence of major cardiovascular events in healthy individuals aged ≥60 years (women) or ≥50 years (men) with normal LDL-C levels but elevated hsCRP levels, demonstrating its efficacy in primary prevention of cardiovascular disease.

Rosuvastatin was well tolerated, with most side effects being mild to moderate, and it effectively lowered both LDL-C and hsCRP levels, although the exact mechanism of its benefits remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: a review of its use in the prevention of cardiovascular disease in apparently healthy women or men with normal LDL-C levels and elevated hsCRP levels. Carter, NJ.[2015]

In a study of 22 youths treated with risperidone for an average of 4.9 months, there was a significant average weight gain of 7.0 kg, indicating a notable side effect of this medication.

While no significant changes in triglyceride or cholesterol levels were observed overall, weight gain was strongly correlated with triglyceride level changes, suggesting the need for regular monitoring of these parameters in children and adolescents on risperidone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Triglyceride, cholesterol and weight changes among risperidone-treated youths. A retrospective study. Martin, A., L'Ecuyer, S.[2019]

Rosuvastatin, currently in phase III clinical trials, shows promise in significantly lowering total cholesterol and LDL cholesterol levels in patients with high cholesterol, potentially more effectively than other statins.

However, there is not enough evidence to assess the safety of rosuvastatin or its impact on heart-related health outcomes, indicating that further research is needed to fully understand its benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin: do we need another statin? Ho, C.[2010]

Statins, which inhibit the enzyme HMG-CoA reductase, have been proven to be both safe and effective in treating hyperlipidemia in adults and may also benefit children with hypercholesterolemia.

In studies lasting up to three years, six different statins (lovastatin, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin) have shown significant reductions in total cholesterol and LDL cholesterol levels in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Use of statins in children]. Tapia Ceballos, L., Picazo Angelín, B., Ruiz García, C.[2019]

In a study of 13 adolescents with psychotic disorders, the prevalence of metabolic syndrome increased from 23% before starting clozapine to 46.2% after more than 6 months of treatment, indicating a significant risk associated with the medication.

Clozapine was effective in reducing symptoms of psychosis, as shown by a significant decrease in PANSS scores, particularly in those who developed metabolic syndrome during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic Disturbances, Side Effect Profile and Effectiveness of Clozapine in Adolescents. Grover, S., Hazari, N., Chakrabarti, S., et al.[2020]

Rosuvastatin is a powerful statin that effectively lowers total cholesterol, LDL cholesterol, triglycerides, and apolipoprotein B, potentially achieving better results than other statins, making it a promising option for treating hyperlipidaemia.

It is well tolerated with a low risk of liver or muscle toxicity, and its once-daily dosing and minimal drug interactions make it a convenient choice for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical rationale for rosuvastatin, a potent new HMG-CoA reductase inhibitor. Hanefeld, M.[2015]

In a study of 82 children and adolescents treated with clozapine for severe psychiatric disorders, 95% were discharged on the medication, indicating its potential effectiveness in this population.

Common adverse events included sedation (26.8%) and sialorrhea (17.1%), highlighting the importance of careful monitoring for side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Multicenter Evaluation of Clozapine Use in Pediatric Patients Admitted for Acute Psychiatric Hospitalization. Steinauer, LM., Leung, JG., Burkey, BW., et al.[2019]

Rosuvastatin is a potent statin that significantly reduces LDL cholesterol by 52-63% at doses of 10-40 mg, outperforming other statins like atorvastatin and simvastatin in lowering LDL levels.

It is well tolerated and has a safety profile similar to other statins, making it a suitable option for patients with dyslipidemia, including those with hypertriglyceridemia or diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin--a highly effective new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor: review of clinical trial data at 10-40 mg doses in dyslipidemic patients. Schuster, H.[2017]

Antipsychotic medications, particularly second and third-generation types, have been shown to be effective in treating psychosis in children and adolescents, but they carry a risk of significant side effects, especially metabolic syndrome.

Clozapine is highlighted as the most effective antipsychotic for both adults and treatment-resistant children and adolescents, with specific guidance provided for managing its side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychopharmacologic treatment of psychosis in children and adolescents: efficacy and management. Kranzler, HN., Cohen, SD.[2014]

In a study of 73 children with Tourette syndrome treated with antipsychotics over an average of 39.6 months, 45% developed lipid abnormalities, indicating a significant risk of metabolic side effects associated with these medications.

While neurologic complications were rare, occurring in only 3 out of 73 children, the findings highlight the importance of regular monitoring of growth and lipid profiles to manage the risks of antipsychotic treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications of antipsychotic therapy in children with tourette syndrome. Pringsheim, T., Pearce, M.[2010]

Rosuvastatin, a commonly prescribed medication for high cholesterol, is generally safe but can lead to rare and serious side effects, such as ischaemic colitis.

In a case study of a 64-year-old woman, ischaemic colitis was diagnosed after starting rosuvastatin, and her symptoms resolved completely after discontinuing the drug, highlighting the need for awareness of this potential adverse reaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman. Tan, J., Pretorius, CF., Flanagan, PV., et al.[2021]

In a study of 502 patients with primary hypercholesterolemia, rosuvastatin (5 mg and 10 mg) significantly reduced LDL cholesterol levels by 42% and 49%, respectively, outperforming pravastatin and simvastatin, which reduced LDL-C by 28% and 37%.

Rosuvastatin 10 mg achieved National Cholesterol Education Program (NCEP) treatment goals in 87% of patients, demonstrating its superior efficacy compared to pravastatin (53%) and simvastatin (64%), while all treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rosuvastatin demonstrates greater reduction of low-density lipoprotein cholesterol compared with pravastatin and simvastatin in hypercholesterolaemic patients: a randomized, double-blind study. Paoletti, R., Fahmy, M., Mahla, G., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/20223367/

Efficacy and safety of rosuvastatin therapy for children with ... Conclusions: In children with familial hypercholesterolemia, rosuvastatin 20 mg daily reduced LDL-C by 50%. Nonetheless, only 40% attained the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28838366/

Efficacy of Rosuvastatin in Children With Homozygous ... Conclusions: This first-ever pediatric HoFH statin trial demonstrated safe and effective LDL-C reduction with rosuvastatin 20 mg alone or added ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0735109710000823

Efficacy and Safety of Rosuvastatin Therapy for Children ... Rosuvastatin 5, 10, and 20 mg once daily lowered LDL-C by 38%, 45%, and 50%, respectively, and 40% of participants reached an LDL-C goal of <110 mg/dl.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02226198

A Study to Evaluate the Efficacy and Safety of Rosuvastatin ... The study is designed to assess the efficacy of rosuvastatin 20 mg compared to placebo on lipids, lipoproteins and apolipoproteins in pediatric patients with ...

5. jacc.org jacc.org/doi/abs/10.1016/j.jacc.2009.10.042

Efficacy and Safety of Rosuvastatin Therapy for Children ... Compared with placebo, rosuvastatin 5, 10, and 20 mg reduced LDL-C by 38%, 45%, and 50%, respectively (p < 0.001 for each group vs. placebo). With a maximum ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/021366s043s044lbl.pdf

Crestor - accessdata.fda.gov The safety and effectiveness of CRESTOR as an adjunct to diet to reduce LDL-C have been established in pediatric patients 8 years of age and older with HeFH.

7. mayoclinic.org mayoclinic.org/drugs-supplements/rosuvastatin-oral-route/description/drg-20065889

Rosuvastatin (oral route) - Side effects & dosage However, safety and efficacy have not been established in children younger than 7 years of age. Geriatric. Appropriate studies performed to date ...

8. astrazeneca.ca astrazeneca.ca/content/dam/az-ca/downloads/productinformation/crestor-product-monograph-en.pdf

crestor-product-monograph-en.pdf Pediatrics (10 to <18 years): Based on the data submitted and reviewed by Health Canada, the safety and efficacy of CRESTOR in pediatric ...

9. drugs.com drugs.com/rosuvastatin.html

Rosuvastatin: Uses, Dosage, Side Effects, Warnings Only Crestor tablets are approved for use in children. Generic versions of rosuvastatin tablets and rosuvastatin capsules are not approved for ...