Cancer CachexiaNCT03144128
Vitamin D for Muscle Metabolic Function in Cancer Cachexia
A study testing Vitamin D in people with Cancer Cachexia and Vitamin D Deficiency, run by David Travis Thomas at 1 site in United States.
Trial summary
The proposed study is aimed at examining mitochondrial function as a potential target of action of vitamin D on muscle metabolism, size, and strength in preventing the progression of cachexia. Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- Cancer Cachexia, Vitamin D Deficiency
- What is being tested?
- Vitamin D
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 23 May 2018to 13 Sep 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed stage II-IV lung cancer and be planned for definitive non-surgical therapy.
- Patients may have a history of prior malignancy.
- Mild cancer cachexia, defined by the miniCASCO score of 0-25 points
- Vitamin D insufficiency, defined as 25(OH)D < 32 ng/ml
- Aged 45 to 75 years. Stratified randomization by age
- ECOG performance status ≤ 2 (see Appendix A).
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- Life expectancy of greater than 3 months
- Patients must have normal renal and liver function as defined below:
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine within normal institutional limits OR creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- Able to swallow thin liquids
- No uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active serious infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Uncontrolled cardiac arrhythmia
- Uncontrolled hypertension
- Psychiatric illness or social situation that would preclude compliance with study requirements
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients with untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with treated brain metastasis are eligible for this trial, providing they have completed treatment at least one day prior to registration.
- History of allergic reactions to whey or milk proteins.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with a history of calcium oxalate nephrolithiasis are excluded.
- Patients with a significant history of malabsorption (e.g. celiac sprue, short bowel syndrome, IBD or other, as determined by the treating physician) are excluded.
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- Patients will not be eligible if actively receiving treatment for vitamin D deficiency and have had recent (3 month) history of vitamin D supplementation (>1000 IU) or calcium supplementation (>800mg).
- The following exclusion criteria will avoid the possibility of preexisting muscle impairment: history of congenital myopathies; neurologic disorder involving sequelae of spinal derangement; disk disease or vascular disease; tremor and rigidity.
- Patients will also be excluded if they report lower extremity (LE) surgery or injury to the LE in the past 3 months or a past medical history of primary hyperparathyroidism; or rhabdomyolysis.
- Additional exclusion criteria include participation in a scheduled resistance exercise program 1 month;
- metal implants or other contraindications for the MRI;
- diabetes,
- advanced renal disease,
- uncontrolled hypertension;
- a vitamin D status (25(OH)D) of > 32ng/mL.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Contribution of Vitamin D to Muscle Metabolic Function in Cancer Cachexia
The proposed study is aimed at examining mitochondrial function as a potential target of action of vitamin D on muscle metabolism, size, and strength in preventing the progression of cachexia. This is the first clinical trial designed to understand the effects of vitamin D on muscle metabolic dynamics driving dysfunction in cachectic muscle. Our preliminary data suggest that vitamin D promotes lipid partitioning and muscle metabolic function, which the investigators hypothesize, will mitigate cachexia via improved muscle health and quality that translates into reduced fatigue, and improved patient resilience to multimodal cancer therapy.
Read the detailed description
Vitamin D repletion is linked to improved muscle mitochondrial function, lipid deposition and preservation; however, while vitamin D insufficiency is common in cancer, the mechanistic effects of vitamin D on muscle metabolic health in cancer patients have not been studied. This is important to address because cancer cachexia is characterized by marked muscle wasting, anabolic resistance, ectopic fat infiltration, mitochondrial dysfunction and contributes to decreased survival. With novel strategies to address this knowledge gap, the investigators will use a combination of advanced metabolic analytical approaches with complementary model systems in cell culture and human subjects to understand the biochemical and physiological mechanisms underlying cancer cachexia in relation to the role of vitamin D in conjunction with resistance exercise (RE). By combining analyses of muscle size and local tissue hemodynamics in vivo, metabolomics analyses of muscle tissue and isolated mitochondria, and changes in anabolic cell signaling, lipid metabolism and oxidative capacity of primary muscle cells in vitro, the investigators will identify mechanisms underlying muscle response to vitamin D repletion. Our previous findings, together with data that exercise improves muscle vitamin D storage and retrieval, suggest that vitamin D repletion synergizes with RE to improve muscle metabolic function and protein synthesis. Our overall objective is to examine mitochondrial function and anabolic resistance as potential targets of action of vitamin D on muscle metabolism, size and strength in preventing the progression of cachexia. The aims of this study are to: 1) non-invasively quantify lipid redistribution, local muscle tissue metabolism and muscle mass and strength of cancer patients before and after 12 weeks of double blinded vitamin D repletion with exercise and protein supplementation (VitD) compared to exercise and protein supplementation only (Ctl); 2) determine differences in muscle mitochondrial function in live tissue biopsied from human gastrocnemius from VitD compared to Ctl; and 3) identify mechanisms whereby vitamin D and exercise regulate muscle anabolic signaling and mitochondrial activity in primary human myotube cultures. Our central hypothesis is that vitamin D promotes muscle lipid availability for β-oxidation in response to exercise, thereby preventing lipotoxicity in the muscle and potentially improving anabolic sensitivity in muscle during cancer cachexia. The impact of this project, the first nutrition and exercise study designed as an inexpensive intervention, is to understand the effect of vitamin D on the metabolic and anabolic dynamics which underpin dysfunction in cachectic muscle. If vitamin D promotes lipid partitioning, muscle metabolic function and/or anabolic sensitivity, these adaptations will ultimately improve cancer therapy by combating cancer cachexia. Further, diffuse optical spectroscopy techniques have the potential to identify the minimum effective intervention dose for optimizing metabolic health leading to more practical and individualized lifestyle prescriptions to reduce health care costs.
- Conditions
- Cancer Cachexia, Vitamin D Deficiency
- Being tested
- Vitamin D, Placebo
- Keywords
- vitamin D, muscle, metabolism, cancer cachexia
- Medical subject headings
- Vitamin D Deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin DDietary supplement
5,000IU vitamin D given daily for 12 weeks
PlaceboDietary supplement
Placebo capsules given daily for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Control (Ctl) | Placebo comparator | Standard of Care resistance exercise and timed protein supplementation with placebo capsule daily for 12 weeks Receives: Dietary Supplement: Placebo |
| Vitamin D | Experimental | Standard of Care resistance exercise and timed protein supplementation with 5,000IU vitamin D supplementation daily for 12 weeks Receives: Dietary Supplement: Vitamin D |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-invasive quantification of muscle lipid distribution
MRI/MRS
Measured: Change between Week 0 and Week 12
Local muscle oxygen consumption
Near Infrared Spectroscopy + Diffuse Correlation Spectroscopy measures will be combined to assess changes in local muscle tissue oxygen consumption (VO2 measure)
Measured: Change between Week 0 and Week 12
Muscle Mass
MRI
Measured: Change between Week 0 and Week 12
Muscle Strength
Maximal voluntary contractions and 1-Repetition Maximum will be aggregated to to provide a comprehensive assessment of muscle strength
Measured: Change between Week 0, Week 6, Week 12
Secondary outcomes (6)
Mitochondrial Function in Muscle Fibers in Fresh Muscle Fibers ex vivo
Determine the differences in muscle mitochondrial function in live tissue biopsied from human gastrocnemius from VitD compared to Ctl by measure live tissue oxygen consumption rate. Respiration measures will be combined to assess mitochondrial function
Mitochondrial respiration will be measured by the XF96 Seahorse extracellular flux analyzer
Measured: Experiments will be conducted from tissue collected at week 12 study biopsy
Mitochondrial Function in Muscle Fibers in Fresh Muscle Fibers ex vivo
Determine the differences in muscle mitochondrial function in live tissue biopsied from human gastrocnemius from VitD compared to Ctl by measure live tissue oxygen consumption rate. Fatty acid oxidation measures will be combined to assess mitochondrial function
Fatty acid oxidation will be estimated by monitoring the OCR of cells with no exogenous glucose or glutamine (Gln) ± a specific fatty acid oxidation (FAO) inhibitor, etomoxir (40 µM)
Measured: Experiments will be conducted from tissue collected at week 12 study biopsy
Stable Isotope-Resolved Metabolomics to describe Fatty Acid Metabolism in relationship to other fuel substrates in Fresh Muscle Fibers ex vivo
Determine the relative importance of vitamin D on lipid, amino acid and energy metabolism involving glucose, glutamine, and β-oxidation in intact muscle fibers. We will culture with 13C8-octanoate, 13C6-glucose, or 13C5-Gln and measure metabolite isotopomer distributions to accomplish this goal.
Measured: Experiments will be conducted from live tissue collected at week 12 study biopsy
Utilize cell culture experimentation to understand anabolic signaling in response to vitamin D with or without fiber stretch.
Identify mechanisms whereby vitamin D and RE regulate anabolic signaling in primary human myotube cultures. Changes in signaling pathways associated with hypertrophy, including Akt, mTOR, MAPK, and AMPK, will be measured by phospho-western blot to determine response to calcitriol, palmitate, and stretch treatment in myotubes.
Measured: Experiments will be conducted from tissue collected at week 12 study biopsy
Utilize cell culture experimentation to measure mitochondrial activity in response to vitamin D with or without fiber stretch.
To understand how vitamin D and RE regulate mitochondrial activity in primary human myotube cultures, the investigators will measure extracellular acidification rate (ECAR) in response to calcitriol supplementation. This will be assessed through the addition of CPT-1 inhibitor etomoxir (40 µM) and the ATP-synthase inhibitor oligomycin
Measured: Experiments will be conducted from tissue collected at week 12 study biopsy
Utilize cell culture experimentation to measure mitochondrial activity in response to vitamin D with or without fiber stretch.
Identify mechanisms whereby vitamin D and RE regulate mitochondrial activity in primary human myotube cultures.
The investigators will measure the concentration of ATP in myotubes in response to calcitriol supplementation.
Measured: Experiments will be conducted from tissue collected at week 12 study biopsy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2017
- Study start23 May 2018
- Primary completion13 Sep 2018
- Study completion13 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cancer CachexiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, double-blinded randomized controlled clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- David Travis Thomas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, David Travis Thomas, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03144128
- Sponsor's protocol ID
- MCC-15-LUN-102
- Other IDs
- MCC Protocol #15-1024-F1V
- Status last verified
- Oct 2020
- First submitted
- 20 Mar 2017
- Last updated
- 14 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Contribution of Vitamin D to Muscle Metabolic Function in Cancer Cachexia
- ClinicalTrials.gov ID
- NCT03144128
- Acronym / sponsor ID
- MCC-15-LUN-102
- Conditions
- Cancer Cachexia, Vitamin D Deficiency
- Keywords
- vitamin D, muscle, metabolism, cancer cachexia
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1 participants (actual)
- Lead sponsor
- David Travis ThomasUniversity, hospital or other
- Study start
- 23 May 2018 (actual)
- Primary completion
- 13 Sep 2018 (actual)
- Study completion
- 13 Sep 2018 (actual)
- First posted
- 8 May 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study is aimed at examining mitochondrial function as a potential target of action of vitamin D on muscle metabolism, size, and strength in preventing the progression of cachexia. This is the first clinical trial designed to understand the effects of vitamin D on muscle metabolic dynamics driving dysfunction in cachectic muscle. Our preliminary data suggest that vitamin D promotes lipid partitioning and muscle metabolic function, which the investigators hypothesize, will mitigate cachexia via improved muscle health and quality that translates into reduced fatigue, and improved patient resilience to multimodal cancer therapy.
Detailed description
Vitamin D repletion is linked to improved muscle mitochondrial function, lipid deposition and preservation; however, while vitamin D insufficiency is common in cancer, the mechanistic effects of vitamin D on muscle metabolic health in cancer patients have not been studied. This is important to address because cancer cachexia is characterized by marked muscle wasting, anabolic resistance, ectopic fat infiltration, mitochondrial dysfunction and contributes to decreased survival. With novel strategies to address this knowledge gap, the investigators will use a combination of advanced metabolic analytical approaches with complementary model systems in cell culture and human subjects to understand the biochemical and physiological mechanisms underlying cancer cachexia in relation to the role of vitamin D in conjunction with resistance exercise (RE). By combining analyses of muscle size and local tissue hemodynamics in vivo, metabolomics analyses of muscle tissue and isolated mitochondria, and changes in anabolic cell signaling, lipid metabolism and oxidative capacity of primary muscle cells in vitro, the investigators will identify mechanisms underlying muscle response to vitamin D repletion. Our previous findings, together with data that exercise improves muscle vitamin D storage and retrieval, suggest that vitamin D repletion synergizes with RE to improve muscle metabolic function and protein synthesis. Our overall objective is to examine mitochondrial function and anabolic resistance as potential targets of action of vitamin D on muscle metabolism, size and strength in preventing the progression of cachexia. The aims of this study are to: 1) non-invasively quantify lipid redistribution, local muscle tissue metabolism and muscle mass and strength of cancer patients before and after 12 weeks of double blinded vitamin D repletion with exercise and protein supplementation (VitD) compared to exercise and protein supplementation only (Ctl); 2) determine differences in muscle mitochondrial function in live tissue biopsied from human gastrocnemius from VitD compared to Ctl; and 3) identify mechanisms whereby vitamin D and exercise regulate muscle anabolic signaling and mitochondrial activity in primary human myotube cultures. Our central hypothesis is that vitamin D promotes muscle lipid availability for β-oxidation in response to exercise, thereby preventing lipotoxicity in the muscle and potentially improving anabolic sensitivity in muscle during cancer cachexia. The impact of this project, the first nutrition and exercise study designed as an inexpensive intervention, is to understand the effect of vitamin D on the metabolic and anabolic dynamics which underpin dysfunction in cachectic muscle. If vitamin D promotes lipid partitioning, muscle metabolic function and/or anabolic sensitivity, these adaptations will ultimately improve cancer therapy by combating cancer cachexia. Further, diffuse optical spectroscopy techniques have the potential to identify the minimum effective intervention dose for optimizing metabolic health leading to more practical and individualized lifestyle prescriptions to reduce health care costs.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective, double-blinded randomized controlled clinical trial
| Arm | Type | Receives |
|---|---|---|
| Control (Ctl) | Placebo comparator | Dietary Supplement: PlaceboStandard of Care resistance exercise and timed protein supplementation with placebo capsule daily for 12 weeks |
| Vitamin D | Experimental | Dietary Supplement: Vitamin DStandard of Care resistance exercise and timed protein supplementation with 5,000IU vitamin D supplementation daily for 12 weeks |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Patients must have histologically or cytologically confirmed stage II-IV lung cancer and be planned for definitive non-surgical therapy.
- Patients may have a history of prior malignancy.
- Mild cancer cachexia, defined by the miniCASCO score of 0-25 points
- Vitamin D insufficiency, defined as 25(OH)D < 32 ng/ml
- Aged 45 to 75 years. Stratified randomization by age
Key exclusion criteria (15 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients with untreated brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with treated brain metastasis are eligible for this trial, providing they have completed treatment at least one day prior to registration.
- History of allergic reactions to whey or milk proteins.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients with a history of calcium oxalate nephrolithiasis are excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin D5,000IU vitamin D given daily for 12 weeks | Dietary supplement | Vitamin D |
| PlaceboPlacebo capsules given daily for 12 weeks | Dietary supplement | Control (Ctl) |
Primary outcome
Non-invasive quantification of muscle lipid distribution
Time frame: Change between Week 0 and Week 12
MRI/MRS
Local muscle oxygen consumption
Time frame: Change between Week 0 and Week 12
Near Infrared Spectroscopy + Diffuse Correlation Spectroscopy measures will be combined to assess changes in local muscle tissue oxygen consumption (VO2 measure)
Muscle Mass
Time frame: Change between Week 0 and Week 12
MRI
Muscle Strength
Time frame: Change between Week 0, Week 6, Week 12
Maximal voluntary contractions and 1-Repetition Maximum will be aggregated to to provide a comprehensive assessment of muscle strength
6 secondary outcomes
Mitochondrial Function in Muscle Fibers in Fresh Muscle Fibers ex vivo
Time frame: Experiments will be conducted from tissue collected at week 12 study biopsy
Mitochondrial Function in Muscle Fibers in Fresh Muscle Fibers ex vivo
Time frame: Experiments will be conducted from tissue collected at week 12 study biopsy
Stable Isotope-Resolved Metabolomics to describe Fatty Acid Metabolism in relationship to other fuel substrates in Fresh Muscle Fibers ex vivo
Time frame: Experiments will be conducted from live tissue collected at week 12 study biopsy
Utilize cell culture experimentation to understand anabolic signaling in response to vitamin D with or without fiber stretch.
Time frame: Experiments will be conducted from tissue collected at week 12 study biopsy
Utilize cell culture experimentation to measure mitochondrial activity in response to vitamin D with or without fiber stretch.
Time frame: Experiments will be conducted from tissue collected at week 12 study biopsy
Utilize cell culture experimentation to measure mitochondrial activity in response to vitamin D with or without fiber stretch.
Time frame: Experiments will be conducted from tissue collected at week 12 study biopsy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vitamin D in people with Cancer Cachexia and Vitamin D Deficiency, run by David Travis Thomas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-invasive quantification of muscle lipid distribution (time frame: Change between Week 0 and Week 12). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2020.