Clinical trial NCT03708354: Tocotrienols for Skeletal Muscle Health
Official title: Tocotrienols Supplementation for Postmenopausal Women With Low Muscle Strength
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Dynapenia
Postmenopausal Women
Keywords: skeletal muscle strength
Lead sponsor: Texas Tech University Health Sciences Center
Sponsor class: OTHER
First posted: 2018-10-17
Enrollment: 0
Sex: FEMALE
Minimum age (years): 60
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: dietary supplement
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: lower-body muscle endurance
timeFrame: 24 weeks
Secondary outcomes:
measure: 8-OHdG
timeFrame: 24 weeks
measure: oxylipins
timeFrame: 24 weeks
measure: gut microbiome
timeFrame: 24 weeks
measure: handgrip strength
timeFrame: 24 weels
measure: lower-body muscle strength
timeFrame: 24 weeks
measure: functional performance
timeFrame: 24 weeks
measure: Muscle size of the lower-extremity musculature
timeFrame: 24 weeks
measure: F2-isoprostanes
timeFrame: 24 weeks
measure: TNF-alpha
timeFrame: 24 weeks
measure: hs-CRP
timeFrame: 24 weeks
measure: endocannabinoid
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Lubbock
country: United States
facility: Texas Tech University Health Sciences Center
state: Texas
Study officials:
affiliation: Texas Tech University Health Sciences Center
name: Chwan-Li Shen, PhD
role: PRINCIPAL_INVESTIGATOR
References: