Tocotrienols for Skeletal Muscle Health (VitE-muscle)

Tocotrienols Supplementation for Postmenopausal Women With Low Muscle Strength

Sarcopenia, defined as a reduction in muscle mass and strength, is a major health concern for postmenopausal women. Evidence suggests that lowering inflammation levels is an important strategy to help mitigate age-related muscle dysfunction and loss. In this pilot study, the investigators will study a tocotrienol (vitamin-E isomer) intervention for feasibility and quantify its effects on postmenopausal women with low muscle strength. A double blind, placebo controlled trial will be conducted on fifty-two qualified subjects. The participants will be assigned to placebo or tocotrienols for 24 weeks. All participants will receive an Omron Alvita Optimized Pedometer. The investigators will measure muscular endurance, strength, and size and gut microbiome profiles at 0, 12, and 24 weeks. In addition, the investigators will measure serum and muscle inflammatory levels at 0 and 24 weeks. All data will be analyzed statistically at p<0.05.

Study Overview

• Status: Withdrawn
• Conditions: Postmenopausal Women; Dynapenia
• Intervention / Treatment: Drug: placebo softgel; Drug: DeltaGold® Tocotrienol 70%

Detailed Description

Sarcopenia is a major health issue in postmenopausal women (PMW). The long-term goal is to develop a new strategy featuring a dietary supplement for alleviating sarcopenia in postmenopausal women. The objective is to test a dietary supplement intervention (delta-tocotrienols, TT) for feasibility, and to quantitatively assess its effects on postmenopausal women with sarcopenia. Due to the limited budget, the investigators will not assess appendicular muscle mass in this pilot study and will focus on muscle strength and function. The central hypotheses are that (i) TT supplementation will alleviate age-associated skeletal muscular dysfunction of postmenopausal women with low muscle strength, and (ii) such changes in skeletal muscle are associated with lowered oxidative stress and inflammation wherein the targets are oxylipins (OxL) and endocannabinoids (eCB), and possible modification of gut microbiota. This is a randomized double-blinded placebo-controlled trial. Fifty-two qualified subjects will be assigned to placebo or TT for 24 weeks. There are 4 specific aims (SA) in this study. SA 1 is to evaluate the effects of TT intervention on endurance, strength, function and size of the lower-extremity musculature in PMW with low muscle strength. SA 2 is to measure the effects of TT intervention on oxidative stress and inflammatory levels. SA 3 is to measure the effects of TT intervention on inflammatory OxL and eCB levels in plasma and muscle tissue. SA 4 is to evaluate the effects of TT intervention on abundance and composition of intestinal bacterial in feces. The outcome measures of SA 1 will be assessed at the baseline, after 12 and 24 weeks. The outcome measures of SA 2, SA 3, and SA 4 will be assessed at the baseline and after 24 weeks. In addition, at 0 and 24 weeks, the investigators will monitor (i) compliance by pill count and (ii) changes in lifestyle throughout the study via food intake surveys and physical activity surveys. Descriptive statistics, bivariate tests, and general/generalized linear mixed modeling will be used for the quantitative analysis on the effects of the TT intervention.

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Lubbock, Texas, United States, 79430
      • Texas Tech University Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 58 years to 83 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion criteria:

1. Postmenopausal women (60-85 yr) not on hormone replacement therapy in the past year.
2. Normal liver, kidney, thyroid function (TSH), serum 25-OH vitamin D (≥ 20 ng/ml)-sent to Quest Diagnostic Laboratory.
3. Grip strength weakness (<20 kg).
4. Sedentary -evaluated by using self-administered International Physical Activity Questionnaire (IPAQ) short form.

Exclusion criteria:

1. Serious chronic disease (e.g., unstable CVD, uncontrolled diabetes, uncontrolled hypertension, active cancer, Parkinson's disease).
2. Taking hormone replacement therapy within 3 months before study starts.
3. Taking medications (i.e., steroids) within 3 months before study starts, since steroids could affect muscle function.
4. Taking supplements (i.e., fish oil) that have anti-inflammatory action during the past 3 months.
5. Having dementia or other medical/eating disorder (i.e. currently receiving an appetite stimulant).
6. Self-report of >10% body weight loss in the past month.
7. Taking anticoagulants that may interact with tocotrienols.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control; One 430 mg olive oil softgel daily for 24 weeks. Each placebo softgel of 430 mg olive oil will contain no tocotrienol or tocopherols at detectable levels.	Drug: placebo softgel; One 430 mg olive oil softgel daily for 24 weeks. Each placebo softgel of 430 mg olive oil will contain no tocotrienol or tocopherols at detectable levels.; Other Names: olive oil
Active Comparator: Intervention; One 430 mg tocotrienol softgel daily for 24 weeks. Each tocotrienol softgel (DeltaGold® Tocotrienol 70%) contains 430 mg tocotrienol (90% δ-tocotrienol+10% γ-tocotrienol) with a 70% purity, representing 300 mg tocotrienol.	Drug: DeltaGold® Tocotrienol 70%; Each TT softgel (DeltaGold® Tocotrienol 70%) contains 430 mg TT (90% δ-TT+10% γ-TT) with a 70% purity, representing 300 mg TT.; Other Names: tocotrienol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
lower-body muscle endurance	assessed by 6-min walk test	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
8-OHdG	urine 8-hydroxy-2'-deoxyguanosine	24 weeks
oxylipins	oxylipins levels in plamsa and skeletal muscle biopsy	24 weeks
gut microbiome	abundance and composition of intestine microbiome in feces	24 weeks
handgrip strength	assessed by a hand dynamometer	24 weels
lower-body muscle strength	assessed by isometric knee extension muscle strength	24 weeks
functional performance	assessed by Time Up and Go test	24 weeks
Muscle size of the lower-extremity musculature	cross-sectional area of the rectus femoris assessed using a diagnostic ultrasound device	24 weeks
F2-isoprostanes	F2-isoprostanes in urine	24 weeks
TNF-alpha	Transforming necrosis factor-alpha in urine	24 weeks
hs-CRP	high sensitivity C-reactive protein	24 weeks
endocannabinoid	endocannabinoid levels in plasma and muscle biopsy	24 weeks

Collaborators and Investigators

• Sponsor: Texas Tech University Health Sciences Center
• Investigators: Principal Investigator: Chwan-li Shen, PhD, Texas Tech University Health Sciences Center

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2019
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: October 10, 2018
• First Submitted That Met QC Criteria: October 12, 2018
• First Posted (Actual): October 17, 2018

Study Record Updates

• Last Update Posted (Actual): February 18, 2022
• Last Update Submitted That Met QC Criteria: February 2, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: skeletal muscle strength
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Protective Agents; Micronutrients; Vitamins; Antioxidants; Vitamin E; Tocopherols; Tocotrienols
• Other Study ID Numbers: L19-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No