Annatto-derived GG for Statin-associated Myopathy

Study Overview
=================
Brief Summary
-----------------
To evaluate the effects of 3-months annatto-derived geranylgeraniol (GG) supplementation on statin-associated skeletal muscle health.

Detailed Description
-----------------
Statins are widely prescribed cholesterol-lowering oral drugs. The majority of reported adverse effects due to statin include muscle pain, weakness, cramp, and tiredness. CoQ10 supplementation has been widely used to reduce statin-related muscle complaints. Several human studies have been reported with inconsistent effects of CoQ10 on statin-related symptoms. This study is to investigate the role of 3-month annatto-derived geranylgeraniol (GG) in statin-related muscle outcomes in humans. Qualified subjects will be matched by age, gender, and body weight, and then randomly assigned to a no GG group, a low GG dose group, or a high GG dose group. The outcome measures will be assessed at baseline and after 3 months. Muscle-associated measurements will be recorded using subject questionnaires (also follow-up after 3 and 6 months), muscle performance results, and blood samples. We will monitor the safety of subjects after 3 months. Food intake, physical activity, and medication changes will be recorded at baseline and after 3 months. All data will be analyzed statistically.

Official Title
-----------------
Effect of Annatto-derived Geranylgeraniol (GG) on Statin-associated Myopathy

Conditions
-----------------
Myopathy; Primary

Intervention / Treatment
-----------------
* Dietary Supplement: Placebo
* Dietary Supplement: Low GG
* Dietary Supplement: High GG


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age ≥40 of either sex Statin-treated patients with muscle pain alone or accompanied by other symptoms. Patients currently receiving a statin who developed new-onset myalgias in within 90 day of initiation or a dosage increase Exclusion Criteria: Malignancy or significant neurological or psychiatric disturbances, including alcohol or drug abuse. Woman who is pregnant, breastfeeding, or of childbearing potential and not taking adequate contraceptive precautions. Had CoQ10 supplement one month before starting the study. Genetic musculoskeletal and neurologic disorder known to affect skeletal muscle metabolism Had steroid medication one month before starting the study.

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo group: subject will take one pill (150 mg olive oil) after breakfast and another pill (150 mg olive oil) after dinner | Dietary Supplement: Placebo<br>* 300 mg olive oil<br>|
| Active Comparator: Low GG<br>LOW GG group: subject will take one pill (150 mg olive oil) after breakfast and another pill (150 mg GG) after dinner | Dietary Supplement: Low GG<br>* 150 mg GG<br>|
| Active Comparator: High GG<br>HIGH GG group: subject will take one pill (150 mg GG) after breakfast and another pill (150 mg GG) after dinner | Dietary Supplement: High GG<br>* 300 mg GG<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SAMS-CI | Statin-Associated Muscle Symptom Clinical Index (SAMS-CI) is to assess muscle pain, muscle weakness, tiredness, and cramps. | change in SAMS-CI at 3 months | 
| BPI | Brief Pain Inventory (BPI) is to assess pain and interference of pain with everyday life. | change in BPI at 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lower body isometric strength | Lower body (i.e., predominantly of the quadriceps and hip extensors) isometric strength is measured using a dynamometer | change in lower body isometric strength at 3 months | 
| Functional lower body strength | Functional lower body strength is measured using a loaded 50m walk. | change in functional lower body strength at 3 months | 
| Wall-sit test | Wall-sit test (wall-slide test) is to assess static leg strength and endurance, particularly of the quadriceps and hip extensors | change in wall-sit test at 3 months | 
| Heel raise test | Heel raise test is commonly used to test calf muscle endurance, function, and performance. Single-leg or both-leg raise will be tested while staining on a step bench | change in heel raise test at 3 months | 
| blood biomarkers: serum creatinine kinase activity | Creatine kinase is to assess muscle damage. | change in serum creatinine kinase activity at 3 months | 
| blood biomarkers: myostatin | Myostatin is to assess muscle damage | changes in serum myostatin at 3 months | 
| blood biomarkers: atrogin 1 | atrogin 1 is to assess muscle damage | changes in serum atrogin 1 at 3 months | 
| blood biomarkers: hsCRP | hsCRP is to assess inflammation | changes in serum hsCRP at 3 months | 
| blood biomarker: IL-6 | IL-6 is to assess inflammation | changes in serum IL-6 at 3 months | 
| blood lipid profiles | lipid profiles include total triglycerides, total cholesterol, HDL, and calculated LDL | changes in blood lipid profiles at 3 months | 
| plasma menaquinone-4 (MK4) + menaquinone-4 (MK7) | MK4 and MK4 are vitamin K2 homologues and are measured by HPLC | changes in plasma MK4+MK7 at 3 months |