Non-Invasive Assessment of Skeletal Muscle Loss in Cancer Patients - Phase II (3MH-2)

The University of Texas System (UT)

Status: Completed

Conditions: Cachexia

Treatments: Biological: (non-radioactive) Oral deuterated 3-methylhistidine (D-3MH)

Study type: Observational

Funder types: Other

Identifiers

NCT01694602

2R44AR054993-02 (U.S. NIH Grant/Contract)

12-064

Details and patient eligibility

About

The overall aim of this research is to develop a non-invasive approach to evaluate the production of 3-methylhistidine (3MH)in cancer patients, as a potential means of determining which patients are at high risk for future development of cancer induced skeletal muscle atrophy.

Rationale: The approach is based on the hypothesis that after an oral dose of deuterated 3-methylhistidine (D-3MH), the slope of the terminal portion of the decay curve (> 12 hours post-dosing) for the tracer/tracee (D-3MH/3MH) in the free 3MH pool is proportional to the rate constant for myofibrillar protein degradation and can be determined from spot urine samples.

Full description

The long-term objective of this research is to develop a non-invasive approach for assessment of de novo 3MH production in cancer patients early in the course of the disease as a way of assessing which patients are at high risk for future development of skeletal muscle atrophy. The approach is based on: 1) the known increase in de novo production of 3-methylhistidine (3MH) from muscle protein breakdown in said patients as a consequence of their unique disease-host interactions, and 2) earlier demonstration that de novo 3MH production can be measured in vivo using isotope dilution.

During this Phase-II project, we propose to conduct a statistically powerful prospective investigation to demonstrate that measurement of the slope of the terminal decay curve (rate constant) with our approach in newly diagnosed cancer patients predicts future development of muscle wasting. We expect the outcome of the combined Phase-I and Phase-II research to lead to the early identification of elevated muscle catabolism in at-risk patients so that medical intervention can prevent future muscle atrophy.

Enrollment: 8 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• (1) histological or cytological evidence of NSCLC without curative options;
• (2) over 18 years of age;
• (3) patient reported weight loss of ≤5% of usual body weight in the last 6 months;
• (4) life expectancy of greater than 6 months based on the judgement of treating physician;
• (5) serum creatinine ≤1.5 times the upper limit of normal; and
• (6) willing and able to give informed consent.

Exclusion criteria

• 1. malabsorption, intractable vomiting or gastrointestinal obstruction
• 2. congestive heart failure
• 3. edema or ascites
• 4. liver function test results that will preclude administration of prescribed therapy
• 5. pregnant, nursing, or, if of child-bearing age, unwilling to use contraceptives

Trial design

8 participants in 1 patient group

Newly Diagnosed NSCLC patients

Description:

In this study, newly diagnosed NSCLC patients who are not candidates for curative resection, will receive a (non-radioactive) oral dose of deuterated 3-methylhistidine (D-3MH).

Treatment:

Biological: (non-radioactive) Oral deuterated 3-methylhistidine (D-3MH)