Clinical trial NCT06077734: Muscle Stem Cell Quality in Atrophy
Official title: In Vitro Quality Assessment of Myogenic Stem Cells in Multiple Patient Groups With Confirmed Skeletal Muscle Atrophy to Study Their Potential for Autologous Stem Cell Therapy
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Muscle Weakness
Atrophy, Muscle
Cachexia
Sarcopenia
Stem Cell Transplantation
Mesenchymal Stem Cells
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2023-10-11
Enrollment: 80
Sex: ALL
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Two study populations are included in this study. The Muscle Impaired Elderly (MIE) are considered elderly who struggle with muscle weakness. MIE is used as a substitute group for sarcopenia as their muscle weakness and daily impairments are confirmed, but confirmation via medical imaging lacks. Sarcopenia is multifactorial and the balance between nutrition and activity is disturbed.

Cachexia is defined as an ongoing loss of skeletal muscle mass due to an illness that cannot be reversed by conventional nutrition and/or exercise. Lung cancer cachexia is a group where non-small cell lung cancer is confirmed along with non-intentional weight loss.

Both groups will be compared to a Control group consisting of eldery undergoing knee/hip/back surgery but are otherwise considered healthy.

Brief summary: The goal of this clinical trial is to compare the quality of mesoangioblasts isolated from various patient groups suffering from muscle atrophy. This study includes cancer cachexia and muscle-impaired elderly and a control group of the same age.

The quality will be defined on these following outcomes:

* The number and distribution of the mesoangioblasts in a muscle biopsy to define if there are sufficient mesoangioblasts to start a culture.
* The proliferation capacity to define if we can culture them the numbers required for systemic treatment.
* The myogenic capacity to define if the mesoangioblasts are sufficiently capable to generate muscle fibres.

Participants will:

* Undergo a muscle biopsy (needle biopsy or rest material from surgery, \~50mg)
* Donate blood (\~20 ml)
* Fill in SARC-F questionnaire (evaluate sarcopenia score)
* Fill in SQUASH questionnaire (evaluate physical activity of previous week) Researchers will compare groups (muscle-impaired elderly vs control; cancer cachexia vs control) to see if there is a difference regarding quality. These results will define the potential of autologous mesoangioblast therapy within these groups.

Detailed description: No effective treatment is available for the loss of muscle tissue in non-genetic muscle diseases such as (cancer) cachexia and sarcopenia. Such a treatment would improve the quality of life, therapy success, and independency of these patients. The administration of healthy autologous muscle stem cells, called mesoangioblasts, that lead to muscle regeneration and increased muscle mass and function could be a novel therapeutic strategy to achieve this. A prerequisite is that the therapeutic potential of these mesoangioblasts is sufficient. Therefore, the main aim of this study is to assess this potential for mesoangioblasts of patients with lung cancer cachexia and with sarcopenia and determine the effect the cancer or age might have on the therapeutic potential.

This study is part of a larger project, called Generate Your Muscle (GYM), which aims to develop and commercially produce a stem cell therapy for recovery of muscle mass and strength in patients with genetic and non-genetic muscle disease and muscle breakdown. This will be achieved by administering large numbers of autologous mesoangioblasts (MABs) as an Advanced Therapy Medicinal Product (asCTMP) in the arteries, which will migrate to the damaged muscle, thereby restoring muscle mass and function. This strategy can only be successful for patients suffering from cachexia or sarcopenia, if these patients have enough mesoangioblasts, if these MABs can proliferate into the numbers requested for systemic treatment, if the energy capacity of the MABs is sufficient and if these mesoangioblasts still have a high myogenic potential. The aim of this study is to determine these parameters for patients with cancer cachexia or sarcopenia, as we know that they can be affected by the underlying condition. They will be compared to age-matched controls. If positive, the MABs will qualify as asCTMP for a clinical trial in a follow-up study.

Eligibility criteria: Inclusion Criteria:

Lung cancer cachexia:

* Diagnosed with NSCLC, stage III-IV
* Diagnosed with cachexia (\>5% unintentional body weight loss in past six months, \>2% body weight loss with BMI \<20, or skeletal muscle index for males \<7.26 kg/m2; females \<5.45 kg/m2)
* Age 50-60 or 60-70
* Written informed consent

Patient group: MIE

* Scheduled for total hip, knee, or back surgery
* Age 60-70 or 70-80 year
* Written informed consent

Controls

* Patients with scheduled knee-, hip-, and back surgery
* Age 50-60, 60-70, and 70-80 year
* Age and sex-matched to patient groups
* Written informed consent

Exclusion Criteria:

* No filled-in IC
* Suffering from a muscular dystrophy or other disease known to affect muscle morphology or function
* Have a weekly alcohol intake of ≥ 35 units (men) or ≥ 24 units (women)
* Ongoing participation in other intervention clinical trials
* Major surgery of the muscle within 4 weeks of the visit unrelated to the study
* Patients unable and/or unwilling to comply with treatment and study instructions
* Any other factor that in the opinion of the investigator excludes the patient from the study

Primary outcomes:
measure: Number of mesoangioblasts ex vivo isolated from muscle biopsy
timeFrame: 1 day
measure: Proliferation capacity of mesoangioblasts in vitro
timeFrame: 1 day
measure: Myogenic capacity of mesoangioblasts in vitro
timeFrame: 1 day
measure: Distribution of mesoangioblasts in a muscle biopsy
timeFrame: 1 day
Secondary outcomes:
measure: Homing potential of mesoangioblasts in vitro
timeFrame: 1 day
measure: ATP production of mesoangioblasts in vitro
timeFrame: 1 day
measure: Difference in myogenic potential of mesoangioblasts and satellite cells in vitro
timeFrame: 1 day
Other outcomes:
Locations:
Study officials:
References: