Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05284149 |
| Other study ID # |
202100881A3 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 15, 2022 |
| Est. completion date |
February 15, 2024 |
Study information
| Verified date |
March 2022 |
| Source |
Chang Gung Memorial Hospital |
| Contact |
Yu-Ching Lin, MD |
| Phone |
+886-975366386 |
| Email |
yuching1221[@]gmail.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Sarcopenia has now been officially recognized as a muscle disease related to aging, which may
increase the risk of falls and fractures and both heart and respiratory diseases in the
elderly. Sarcopenia causes inconvenience in the elderly, affecting their quality of life and
often requiring long-term care or even resulting in death. Moreover, the elderly often
encountered malnutrition due to inadequate nutrient intake and scarce nutrient diversity.
Furthermore, malnutrition is often one of the leading causes of sarcopenia. Therefore,
effective nutritional supplementation is essential to improve or prevent muscle loss for the
elderly.
Cordyceps sinensis is a well-known valuable traditional Chinese medicine and Hirsutella
sinensis was an asexual strain of Cordyceps sinensis. Researchers have found that Hirsutella
sinensis can help to increase connection between gastrocnemius muscle fibers and spinal nerve
under the amyotrophic lateral sclerosis animal disease model. However, culturing conditions
for Hirsutella sinensis are extremely difficult and long, one of the key culturing condition
is the temperature, must be maintaining at 16-20℃for 45 days. Fortunately, Grape King Biotech
has core technology using liquid fermentation which greatly shortened the cultivation time,
thus, providing sufficient and safe products to patients.
The investigators designed a randomized placebo-controlled study first to investigate the
relationship and clinical impact Hirsutella Sinensis had on muscle mass and function in the
elderly. Second, investigate the metabolic impact Hirsutella Sinensis had on muscle mass.
Description:
In 1988, Irwin Rosenberg first proposed the term "Sarcopenia" for sarcopenia, which refers to
the amount of muscle loss with age. In 2007, the European Working Group on Sarcopenia in
Older People (EWGSOP) reached a consensus of three criteria for aging-related sarcopenia:
reduced muscle mass after 65 years of age (60 or 65 years according to the criteria set by
each country), weakening of muscle strength (using grip strength), and physiological
performance (using walking speed)
Sarcopenia has now been officially recognized as a muscle disease related to aging, which may
increase the risk of falls and fractures and both heart and respiratory diseases in the
elderly. Sarcopenia causes inconvenience in the elderly, affecting their quality of life and
often requiring long-term care or even resulting in death. Moreover, there is now
considerable evidence that muscle and bone have common genetic, nutritional, lifestyle, and
hormonal determinants. Besides, muscle and bone interact with each other to impact bone
strength. A possible mechanism is the dynamic loading arises from muscle contractions and the
ground impact during weight-bearing activities. In 2009, the term "sarco-osteopenia" was
coined to emphasize that both weak bones and weak muscles may contribute to fractures in the
elderly. Therefore, treatments related to increasing muscle mass are essential for the
elderly to reduce adverse clinical outcomes such as falls and fractures. At present, the most
efficient treatment is adequate nutrient intake.
The elderly often encountered malnutrition due to inadequate nutrient intake and scarce
nutrient diversity. While malnutrition is often one of the leading causes of sarcopenia.
Therefore, effective nutritional supplementation is essential for the elderly. Efficient
nutrient supply will improve the symptoms of sarcopenia patients and improve the quality of
life. As Taiwan gradually enters the advanced age society, sarcopenia in the elderly is
inevitable. Preventing and treating aging-related muscle loss is becoming a crucial issue
that everyone must face. However, there is still a scarcely known nutrient supplement that
effectively improves muscle health in the elderly. Moreover, to increase the wiliness of the
elderly in taking nutrient supplements, the nutrient supplements must be safe and easily
assessable nutrient supplement and do not require a physician prescription. In the Asian
population, elderlies incline to Chinese medicine supplements.
Cordyceps sinensis is a well-known valuable traditional Chinese medicine. It is the
fungi-insect complex from Clavicipitacease and Cordyceps sinensis (Berk.) Sacc. parasitic on
the Heptaidae insects' larvae. Cordyceps sinensis are mainly distributed in the high-mountain
areas like Tibet, Sichuan, Qinghai, and Gansu. The traditional Chinese medicine of Cordyceps
sinensis have recorded its beneficial effects in kidney and lung, replenishing essence, cough
relief and reducing sputum. In the 1990s, a group of female marathon runners led by Mr. Ma
Jun-ren, commonly known as Ma family army, trained several world-class middle- and
long-distance runner which broke 66 domestic and international records in many competitions.
There has been suggestion of his secret performance-enhancing recipe, which includes the
combination of Cordyceps, turtle essence and other healthcare products to the athletes' diet.
This recipe sets off the Cordyceps market demand once more in China. Enormous Cordyceps were
harvested and sold at the same time for research and development. The price of naturally
found cordyceps become so scarce that the end-price is almost equivalent to the gold. At the
same time period, a total of 22 asexual strains involving 13 genera were isolated from the
Cordyceps fruiting bodies collected from different regions. Molecular identification of rDNA
ITS region and RAPD molecular markers from the fruiting bodies were detailly compared to
finally confirmed that Hirsutella sinensis was an asexual strain of Cordyceps sinensis.
Researchers have found that Hirsutella sinensis has many benefits in anti-inflammatory,
anti-liver cancer activity, reduces tetrachloride damage, immune regulation, improves
Bleomycin-induced lung fibrosis, aristolochic acid or cisplatin induced Kidney damage… and
more. More importantly, study have found that Hirsutella sinensis can help to increase
connection between gastrocnemius muscle fibers and spinal nerve under the amyotrophic lateral
sclerosis animal disease model. However, culturing conditions for Hirsutella sinensis are
extremely difficult and long, one of the key culturing condition is the temperature, must be
maintaining at 16-20℃ for 45 days. Fortunately, Grape King Biotech has core technology using
liquid fermentation which greatly shortened the cultivation time, thus, providing sufficient
and safe products to patients.
The investigators hypothesis that Hirsutella Sinensis may be able to increase both muscle
mass and function in the elderly. The investigators believed that improving the muscle mass
and function in the elderly may improve the elderly with sarcopenia and prevent the elderly
from having sarcopenia. Moreover, it is vital to investigate the metabolic muscle change in
the elderly under Hirsutella Sinensis nutrient supplement. This will allow the investigators
to further understand the mechanism behind Hirsutella Sinensis had on muscle mass and
function.
Specific aims The investigators designed a randomized placebo-controlled study first to
investigate the relationship and clinical impact Hirsutella Sinensis had on muscle mass and
function in the elderly. Second, investigate the metabolic impact Hirsutella Sinensis had on
muscle mass.
2.0 Material and method
2.1.1 Research design This proposal aims to perform a comprehensive analysis of the
Hirsutella Sinensis nutrient supplement to improve muscle mass and function. This study
comprises an interventional clinical trial that will recruit 100 elderly individuals with
either sarcopenia or absence of sarcopenia. All elderly will be receiving clinical,
laboratory, and imaging evaluation (in 6, 12 months) to compare the outcome between elderly
with and without Hirsutella Sinensis nutrient supplements. This study comprised of
comprehensive evaluation of nutrition status, muscle health status and muscle metabolic
status for each participant. Furthermore, a detailed metabolomic analysis will be performed
on these elderlies to understand the possible mechanism for muscle mass changes and function
in the elderly receiving Hirsutella Sinensis nutrient supplements. Figure 1 depict the
outline of this study.
2.1 Subjects:
2.1.1 Study duration and subjects number This randomized control study will be conducted in 2
years. The investigators expect to recruit 100 participants with age ≥ 50 years old. Enrolled
participants will be randomly divided into Hirsutella Sinensis nutrient supplement (H.S.
suppl.) or a placebo group according to a standard randomization procedure (1:1). The
medication will be mailed to the participants by a third party.
All participants will have two different follow-up periods (6, 12 months). These follow-ups
included clinical, laboratory, and imaging studies to analyze muscle health changes after
receiving Hirsutella Sinensis nutrient supplement.
2.1.2 The inclusion criteria As previously described
2.2 Clinical examinations The complete outline of clinical nutrition evaluation, bone
fragility evaluation and muscle health evaluation were described in Figure 2.
Figure 2. The outline of clinical assessment
Clinicopathological data:
Clinicopathological data were collected, including age, gender, body height, body weight and
waist circumference. Subjects were also asked to list all comorbidities and all current
medications. Participants were considered smokers if they currently smoked tobacco or had
smoked in the past. Participants were considered alcohol drinkers if they reported consuming
alcohol four or more times per week.
Clinical nutrition evaluation:
The nutrition indexes were evaluated using anthropometric method (including the body mass
index (BMI)), clinical assessment method (Mini-Nutritional Assessment sheet) and laboratory
methods (CBC/DC, lipid profile and albumin).
Muscle health examinations Muscle health status evaluation, including total body composition
analysis, handgrip strength (HS) test, and Five-Times-Sit-to-Stand (FTSTS) test. Total body
composition analysis may provide us with detailed quantification of fat and muscle of the
entire body and different regions of interest. Furthermore, the combination of handgrip
strength and Five-Times-Sit-to-Stand tests enables us to understand each participant's muscle
function.
Total body composition analysis for muscle mass evaluation:
All the scans were performed using a dual-energy fan-beam X-ray absorptiometry.
Handgrip strength for muscle strength evaluation:
Muscle strength was determined by HS, measured by using a dynamometer.
Five-Times-Sit-to-Stand tests for physical performance evaluation:
The FTSTS test was performed in a quiet room and used a standard chair without armrests. The
faster of the 2 trials was used as the FTSTS score.
2.3 Metabolomics examinations The blood sample for metabolomic examination will be taken at
the same day as the DXA image study.
B. LC-TOFMS analysis 1a. For global metabolites analysis Liquid chromatographic separation
will be achieved on a 100 mm×2.1 mm Acquity 1.7 μm C18 column (Waters Corp; Milford, MA, USA)
using a ACQUITY TM Ultra Performance Liquid Chromatography system (Waters, USA).
1b. Mass spectrometry Mass spectrometry will be performed on a Waters Q TOFMS or Agilent Q
TOF operated in positive or negative ion mode.
C. Ultra-performance liquid chromatography (UPLC)-based amino acid measurement The plasma
samples are collected and stored at -80°C until assayed. The AQC derivatization reagent was
obtained from the Waters Corporation (Milford, MA, USA).
2.4 Nutrient supplements Enrolled participants will be randomly divided into Hirsutella
Sinensis nutrient supplement (H.S. suppl.) or a placebo group according to a standard
randomization procedure (1:1). The medication will be mailed to the participants by a third
party. Hirsutella Sinensis and placebo nutrient supplement pills will be identical in
appearance. Nutrient supplement pills will be taken for six months.
Composition of Hirsutella Sinensis nutrient supplements: whey protein, modified starch,
non-dairy creamer, roux, Hirsutella Sinensis mycelium, maltodextrin, salt, glutamate, flavor
enhancers, vegetable oil, lactose, hydrolyzed vegetable protein, onion powder, chicken
flavour, locust bean gum, turmeric powder.
Composition of placebo: whey protein, modified starch, non-dairy creamer, roux, maltodextrin,
salt, glutamate, flavour enhancers, vegetable oil, lactose, hydrolyzed vegetable protein,
onion powder, chicken flavour, locust bean gum, turmeric powder.
Suggested use: 1 sachet (38 g) per day, add 1 sachet of nutrient supplements to 140 mL of hot
water, stir well and drink carefully.
Statistical analysis To assess the association of Hirsutella sinensis nutrient supplements
had on muscle health and muscle metabolism, Pearson correlation was used for analysis. To
analyze the effect of several covariates on muscle health, stepwise logistic regression
analysis was applied with adjustments for age, BMI, number of co-morbidities, smoking status,
and nutritional status. Logistic regression model and t-test will be applied to analysis the
effect of the impact of efficient Hirsutella sinensis nutrient supplements had on improving
muscle health.
2.5 Potential difficulties
2.5.1 Concern of DXA safety and participant comfort This study will follow the general DXA
safety rules with standard protocols. The participant with DXA contraindication will not be
included into this study.
2.5.2 Supports on the particpants' enrollment The elderly population of interest included all
those aged 60 years or more who were registered as residents of an administrative
neighborhood ("Li") of the North District, Keelung City, Taiwan. In the previous study, the
investigators have understand the prevalence of sarcopenia is about 20~40% in the Keelung
community. Thus, the recruitment of elderlies with or without sarcopenia will not be a big
obstacle in this study.
First year AIMs: Study the effect of Hirsutella sinensis nutrient supplements had on muscle
health.
Second year AIMs: Study the metabolomic alternation in muscle after taking Hirsutella
sinensis nutrient supplements
3.1 Expected schedule
The First Year:
AIMs: Study the effect of Hirsutella sinensis nutrient supplements had on muscle health
A cross-sectional study on: 1. The relationship between Hirsutella sinensis with muscle mass
and function. 2. Compared the improvement of muscle health between participants with and
without sarcopenia.
Baseline clinical, laboratory and image data will be collected in 100 participants (Table 1)
The Second Year:
AIMs: Study the metabolomic alternation in muscle after taking Hirsutella sinensis nutrient
supplements
A cohort study on the metabolomic change in muscle after receiving Hirsutella sinensis.
One year follow-up clinical and image data will be collected in 100 participants.
