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

Trial Summary

What is the purpose of this trial?

Single center, open-label, prospective investigation to quantify the effects hepatocellular fat has on hepatic statin transport and response in children and adolescents in obese and non-obese children and adolescents 8-21 years of age with normal, wild-type SLCO1B1 c.521TT genotype that are dosed rosuvastatin

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.

What data supports the effectiveness of the drug Rosuvastatin for high cholesterol in children?

Research shows that Rosuvastatin, a type of statin, is effective in lowering bad cholesterol (LDL-C) levels in both adults and children. Studies have demonstrated that it can significantly reduce cholesterol levels, making it a potentially beneficial treatment for children with high cholesterol. ^{1 2 3 4 5}

Is rosuvastatin safe for use in humans?

Rosuvastatin is generally considered safe with mostly acceptable side effects, but rare serious side effects like ischaemic colitis (inflammation of the colon due to reduced blood flow) have been reported. It is well tolerated with no evidence of liver or muscle toxicity in preliminary studies. ^{1 3 5 6 7}

How is the drug Rosuvastatin different from other treatments for high cholesterol in children?

Rosuvastatin is unique because it is a statin, which works by blocking a specific enzyme in the liver to reduce cholesterol production, making it effective in lowering 'bad' cholesterol (LDL) levels. Unlike some other treatments, it is specifically designed to target cholesterol production, which can be particularly beneficial for children with high cholesterol. ^{8 9 10 11 12}

Eligibility Criteria

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)

Provide informed permission-assent (<18 yrs.) or consent (≥18 yrs.)

I am between 8 and 21 years old.

Exclusion Criteria

I cannot swallow pills.

Pregnancy

Non-fasting

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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 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]

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]

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]

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]

References

1. New Zealand 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. [2015]

2. Spain pubmed.ncbi.nlm.nih.gov

[Use of statins in children]. [2019]

3. England 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. [2019]

4. Switzerland 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. [2017]

5. India pubmed.ncbi.nlm.nih.gov

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

6. Canada pubmed.ncbi.nlm.nih.gov

Rosuvastatin: do we need another statin? [2010]

7. England pubmed.ncbi.nlm.nih.gov

Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Triglyceride, cholesterol and weight changes among risperidone-treated youths. A retrospective study. [2019]

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

Psychopharmacologic treatment of psychosis in children and adolescents: efficacy and management. [2014]

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

Complications of antipsychotic therapy in children with tourette syndrome. [2010]

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

Metabolic Disturbances, Side Effect Profile and Effectiveness of Clozapine in Adolescents. [2020]

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

A Retrospective Multicenter Evaluation of Clozapine Use in Pediatric Patients Admitted for Acute Psychiatric Hospitalization. [2019]