Annatto-derived GG for Statin-associated Myopathy

(GG-statin Trial)

Overseen By Chwan-Li (Leslie) Shen, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Texas Tech University Health Sciences Center

Must be taking: Statins

Must not be taking: CoQ10, Steroids

Disqualifiers: Malignancy, Neurological, Psychiatric, others

Compensation: Varies

Number of Visits: 2

Duration: 12 weeks

95 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a supplement derived from annatto, called geranylgeraniol (GG), to determine its effectiveness in alleviating muscle pain caused by statin medications. Statins lower cholesterol but can sometimes lead to muscle aches. Participants will be divided into three groups: one receiving a high dose of GG, another a low dose, and a third receiving a placebo (a pill with no active ingredient). Individuals who have started experiencing muscle pain after beginning or increasing their statin dosage in the last 90 days might be suitable for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how GG works in people and measure its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does require that you have not taken CoQ10 or steroid medications one month before starting the study.

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

Research has shown that geranylgeraniol (GG) may alleviate muscle problems caused by statins, which lower cholesterol. These studies have not identified any major safety issues with GG.

In studies where participants took either high or low doses of GG, researchers closely monitored their health, including diet and activity, to ensure no unexpected problems arose. The studies aimed to confirm that GG is well-tolerated, and current evidence suggests it is generally safe.

GG's potential to reduce muscle problems makes it a promising option for people with statin-related muscle issues. This supports the idea that GG might be a safe addition for those experiencing these problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for statin-associated myopathy, which often focus on adjusting statin doses or adding supplements like CoQ10, GG (geranylgeraniol) derived from annatto is being explored as a novel option. Researchers are excited about GG because it offers a new active ingredient that may help mitigate muscle pain without altering the statin's cholesterol-lowering benefits. GG works by replenishing essential compounds in the muscle that statins might deplete, potentially reducing muscle-related side effects while allowing patients to continue benefiting from statins' heart-protective effects.

What evidence suggests that this trial's treatments could be effective for statin-associated myopathy?

Research has shown that geranylgeraniol (GG) might alleviate muscle problems caused by statins, drugs used to lower cholesterol. Studies found that GG could completely reverse muscle fiber loss caused by statins and reduce a protein linked to muscle damage by 65%. This trial will test different doses of GG, with participants receiving either a high or low dose, to determine its effectiveness in reducing these side effects. Overall, evidence supports the idea that GG could be a promising option for those experiencing muscle issues from statins. ^{1 3 4 6 7}

Who Is on the Research Team?

Chwan-Li (Leslie) Shen, PhD

Principal Investigator

Texas Tech Health Science Center

Are You a Good Fit for This Trial?

This trial is for people over 40 who started having muscle pain after beginning or increasing the dosage of statin medication. It's not for pregnant or breastfeeding women, those with genetic muscle metabolism disorders, recent steroid or CoQ10 supplement use, cancer patients, or individuals with major neurological or psychiatric issues.

Inclusion Criteria

You are taking statin medication and experiencing muscle pain with or without other symptoms.

You are taking a statin and recently started having muscle pain within the last 90 days.

You must be at least 40 years old, regardless of whether you are male or female.

Exclusion Criteria

You have a genetic disorder that affects your muscles and nerves.

Woman who is pregnant, breastfeeding, or of childbearing potential and not taking adequate contraceptive precautions

Had steroid medication one month before starting the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive annatto-derived geranylgeraniol (GG) or placebo for 3 months to assess effects on statin-associated muscle symptoms

12 weeks

Baseline visit, monthly check-ins

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 3 and 6 months

3 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• High GG
• Low GG
• Placebo

Trial Overview The study tests if a supplement called annatto-derived geranylgeraniol (GG) can help with muscle pain caused by statins. Participants will receive either a placebo, low dose GG, or high dose GG for three months to see which helps more.

How Is the Trial Designed?

Group I: High GG Active Control 1 Intervention

HIGH GG group: subject will take one pill (150 mg GG) after breakfast and another pill (150 mg GG) after dinner

Group II: Low GG Active Control 1 Intervention

LOW GG group: subject will take one pill (150 mg olive oil) after breakfast and another pill (150 mg GG) after dinner

Group III: Placebo Placebo Group 1 Intervention

Placebo group: subject will take one pill (150 mg olive oil) after breakfast and another pill (150 mg olive oil) after dinner

Who Is Running the Clinical Trial?

Texas Tech University Health Sciences Center

Lead Sponsor

Trials

107

Recruited

11,500+

Published Research Related to This Trial

Cholesfytol®, a dietary supplement combining red yeast rice and olive extract, significantly reduced LDL cholesterol by 23.3% and total cholesterol by 17.5% in a study of 642 hypercholesterolemic patients over 2 months, demonstrating its efficacy as an alternative to statins.

The treatment was well-tolerated, with only 13 patients reporting minor side effects, and it did not induce new-onset statin-associated muscle symptoms (SAMS), making it a safe option for patients with a history of SAMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a combination of red yeast rice and olive extract in hypercholesterolemic patients with and without statin-associated myalgia. Tshongo Muhindo, C., Ahn, SA., Rousseau, MF., et al.[2018]

In a study of 354 patients reporting muscle-related issues from statin therapy, 85% were found to have probable or definite drug adverse effects, with common symptoms including muscle pain (93%), fatigue (88%), and weakness (85%).

Higher potency statins, particularly atorvastatin, were associated with a significantly higher incidence of muscle-related adverse effects compared to lower potency statins, suggesting that switching to lower potency options or discontinuing statins may help alleviate these symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statin-associated muscle-related adverse effects: a case series of 354 patients. Cham, S., Evans, MA., Denenberg, JO., et al.[2022]

A 3-month treatment with atorvastatin at various dosages (10, 40, and 80 mg/day) did not impact maximal muscle performance during exercises, indicating that overall muscle strength was maintained.

However, atorvastatin was associated with reduced muscle excitability and adaptation to fatigue, particularly in muscles with more slow-oxidative fibers, and this was linked to a decreased potassium release after exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of long-term atorvastatin treatment on the electrophysiological and mechanical functions of muscle. Delliaux, S., Steinberg, JG., Lesavre, N., et al.[2019]

In a pilot study involving 14 patients with statin-induced myopathy, the combination of conifer-tree needle polyprenols and CoQ10 was found to be generally safe, with no significant changes in safety parameters, although one patient had to discontinue due to liver enzyme elevations.

Significant improvements in muscle pain and weakness were observed, with some patients reporting complete resolution of symptoms, suggesting potential efficacy that warrants further investigation in larger controlled studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of safety and efficacy of polyprenols in combination with coenzyme Q10 in patients with statin-induced myopathy. Latkovskis, G., Saripo, V., Sokolova, E., et al.[2019]

Statins are effective lipid-lowering drugs widely used to prevent cardiovascular diseases, but they can cause muscular side effects that lead to poor patient compliance and potential discontinuation of treatment.

This review is the first to combine laboratory and clinical findings on statin-induced myotoxicity, aiming to clarify the mechanisms behind these adverse effects and improve safety measures to prevent severe complications like rhabdomyolysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational insight into statin-induced muscle toxicity: from cell culture to clinical studies. Taha, DA., De Moor, CH., Barrett, DA., et al.[2014]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10691100/

Potential role of geranylgeraniol in managing statin ... This opinion paper proposes employing GG to prevent SAMS in pleiotropic statin use, including usage in the post-COVID-19 pandemic era.

2. clinicaltrial.be clinicaltrial.be/en/details/17685?only_recruiting=0&only_eligible=0

Annatto-derived GG for Statin-associated Myopathy - Clini... This study is to investigate the role of 3-month annatto-derived geranylgeraniol (GG) in statin-related muscle outcomes in humans. Qualified ...

3. withpower.com withpower.com/trial/phase-2-muscular-diseases-3-2022-4d0d3

Annatto-derived GG for Statin-associated Myopathy In a study of 354 patients reporting muscle-related issues from statin therapy, 85% were found to have probable or definite drug adverse effects, with common ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405844025000088

Personalized statin therapy: Targeting metabolic processes ... In this review, we explore the potential for customizing therapy by targeting the metabolism of statin medications.

5. researchgate.net researchgate.net/publication/375741246_Potential_role_of_geranylgeraniol_in_managing_statin-associated_muscle_symptoms_a_COVID-19_related_perspective

(PDF) Potential role of geranylgeraniol in managing statin- ... Myopathy is the most common side effect of statins, but it has not been addressed effectively. In anticipation of its wider use as a small ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05312424/annatto-derived-gg-for-statin-associated-myopathy

Annatto-derived GG for Statin-associated Myopathy We will monitor the safety of subjects after 3 months. Food intake, physical activity, and medication changes will be recorded at baseline and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5987243/

Geranylgeraniol Prevents Statin-Dependent Myotoxicity in ... Geranylgeraniol (GGOH) seems a good candidate as few reports showed the beneficial role of the compound in rescuing statin-induced myopathy [6, 7] although work ...