Targeting Muscle-Bone Crosstalk Through Physical Therapy in Cancer Cachexia (PU-PTCC)

September 1, 2026 updated by: Ola Mohamed Elsayed Elgohary, Pharos University in Alexandria

Targeting Muscle-Bone Crosstalk: The Potential of Physical Therapy in Managing Cancer-Induced Cachexia

This study investigates the role of a structured physical therapy (PT) program in managing cancer-induced cachexia (CIC) by targeting muscle-bone crosstalk. Cancer-induced cachexia leads to severe muscle wasting, systemic inflammation, and functional decline, which often limits treatment tolerance and quality of life. While exercise is known to attenuate protein breakdown and modulate muscle-derived cytokines (myokines), its specific impact on muscle-bone signaling in non-metastatic cancer patients undergoing chemotherapy remains underexplored. In this randomized controlled trial (RCT), patients aged 40 to 60 receiving neoadjuvant chemotherapy are assigned to either a control group receiving standard chemotherapy and nutritional counseling, or an experimental group receiving a progressive 3-month exercise program (combining aerobic treadmill training and resistance exercises) alongside standard care. The study aims to evaluate changes in biomarker levels (such as myokines and osteokines) and functional physical outcomes to determine whether targeted exercise can effectively attenuate cachexia and improve rehabilitation outcomes prior to surgery

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

Cancer-induced cachexia (CIC) is a complex multifactorial syndrome characterized by progressive loss of skeletal muscle mass, systemic inflammation, metabolic dysregulation, and functional decline. The physiological interplay between skeletal muscle and bone tissue-known as muscle-bone crosstalk-is regulated through humoral signaling pathways involving myokines and osteokines. Key myokines, such as myostatin (an inhibitor of muscle growth), Interleukin-15 (IL-15, which promotes hypertrophy and fat oxidation), and decorin (which binds to myostatin to promote muscle growth), play pivotal roles in maintaining musculoskeletal homeostasis. Contractile activity during physical exercise can favorably modulate these myokine levels, reducing protein degradation and improving metabolic function. Despite the established systemic benefits of physical exercise, significant knowledge gaps remain regarding the clinical efficacy of structured physical therapy protocols specifically targeting muscle-bone crosstalk in young to middle-aged adults undergoing active cancer treatment. Furthermore, there is limited clinical data quantifying exercise-induced biological changes in circulating myokines (e.g., IL-15, decorin, SPARC) within non-metastatic cancer populations receiving neoadjuvant chemotherapy. This study is designed as a prospective Randomized Controlled Trial (RCT) to evaluate the therapeutic potential of a 3-month exercise intervention in patients aged 40-60 years with Grade 2/3 non-metastatic cancer undergoing neoadjuvant chemotherapy. Eligible participants are randomized into two parallel groups: Control Group: Receives standard care consisting of neoadjuvant chemotherapy accompanied by a structured nutritional support course following cachexia onset. Experimental Group: Receives a progressive 3-month physical therapy program in addition to standard neoadjuvant chemotherapy and nutritional support following cachexia onset. The 3-month physical therapy intervention combines structured aerobic and resistance training protocols: Aerobic Exercise: Treadmill walking performed 3 to 5 times per week (aiming for 150 minutes per week) at a progressive intensity ranging between 40% and 85% of maximum heart rate ($\text{HR}_{\text{max}}$). Resistance Exercise: Progressive strength training performed 2 to 3 times per week consisting of 2 sets of 8 to 10 repetitions at 50% to 70% of 1-repetition maximum (1RM)

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Adults aged 18 years or older.

Confirmed diagnosis of non-metastatic cancer (Grade 2 or Grade 3).

Diagnosed with Cancer-Induced Cachexia (CIC) based on international consensus criteria (weight loss >5% in past 6 months, OR weight loss >2% in individuals with BMI <20 kg/m², OR appendicular skeletal muscle index consistent with sarcopenia).

Scheduled for or currently receiving standard neoadjuvant chemotherapy.

Ability to provide written informed consent and follow a structured physical therapy program.

ECOG Performance Status of 0 to 2.

Exclusion Criteria:

  • Evidence of distant tumor metastasis (Grade 4 cancer).

Severe orthopedic, neurological, or cardiovascular conditions preventing participation in safe physical therapy exercise.

Uncontrolled cardiovascular disease (e.g., unstable angina, recent myocardial infarction, severe cardiac arrhythmias).

Severe bone metastases or pathologic fracture risk that contraindicates weight-bearing exercises.

Prior participation in regular structured aerobic or resistance exercise training within the past 6 months.

Cognitive impairment or psychiatric conditions interfering with treatment compliance or informed consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental Group
Participants receive a structured 3-month physical therapy exercise protocol combining aerobic treadmill training (3-5 days/week) and progressive resistance training (2-3 days/week) alongside standard neoadjuvant chemotherapy and nutritional support.
Other: Structured Physical Therapy Exercise Program

Experimental Group):

A 3-month progressive physical therapy program consisting of aerobic exercise (treadmill walking 3-5 times per week, 150 min/week total, at 40%-85% HRmax) and resistance exercise (2-3 times per week, 2 sets of 8-10 repetitions at 50%-70% 1RM) combined with standard neoadjuvant chemotherapy and nutritional support Standard care comprising neoadjuvant chemotherapy protocols along with routine clinical nutritional support provided upon cachexia diagnosis, with no formal exercise intervention.

Other Names:
  • Standard Care and Nutritional Support
Placebo Comparator: control group
Participants receive standard neoadjuvant chemotherapy accompanied by standard nutritional support following cachexia onset, without participating in the structured physical therapy program
Other: Structured Physical Therapy Exercise Program

Experimental Group):

A 3-month progressive physical therapy program consisting of aerobic exercise (treadmill walking 3-5 times per week, 150 min/week total, at 40%-85% HRmax) and resistance exercise (2-3 times per week, 2 sets of 8-10 repetitions at 50%-70% 1RM) combined with standard neoadjuvant chemotherapy and nutritional support Standard care comprising neoadjuvant chemotherapy protocols along with routine clinical nutritional support provided upon cachexia diagnosis, with no formal exercise intervention.

Other Names:
  • Standard Care and Nutritional Support

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in Serum Biomarkers of Muscle-Bone Crosstalk
Time Frame: 3 month
Serum concentration changes of key muscle-bone crosstalk mediators, specifically Myostatin (MSTN) and Osteocalcin (OCN), evaluated via enzyme-linked immunosorbent assay (ELISA) to assess the impact of physical therapy on cachexia-induced muscle-skeletal degradation.
3 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Muscle Strength
Time Frame: Baseline and 3 months post-intervention
Measured using a hand-grip dynamomete
Baseline and 3 months post-intervention
Change in Bone Mineral Density (BMD
Time Frame: Baseline and 3 months post-intervention
Measured using DEXA scan at the lumbar spine
Baseline and 3 months post-intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Pharos University in Alexandria

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

October 29, 2026

Primary Completion (Estimated)

January 28, 2027

Study Completion (Estimated)

February 2, 2027

Study Registration Dates

First Submitted

August 27, 2026

First Submitted That Met QC Criteria

September 1, 2026

First Posted (Actual)

September 8, 2026

Study Record Updates

Last Update Posted (Actual)

September 8, 2026

Last Update Submitted That Met QC Criteria

September 1, 2026

Last Verified

September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • pharous university cancer ptt

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data (IPD) will not be shared to protect patient confidentiality and clinical privacy.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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