CachexiaPhase 1NCT01962454
A Study to Evaluate a Skeletal-muscle Microbiopsy Technique With Dynamic Proteomic Measurement in Healthy Male Volunteers
A Phase 1 study testing Deuterated Water and Testosterone enanthate in people with Cachexia, run by GlaxoSmithKline at 1 site in United States.
Trial summary
This is a single-blind, randomized placebo-controlled, parallel study, where the study volunteers will be blinded to testosterone/placebo treatment. This study will test a relatively new, less invasive method for collecting muscle tissue to determine if this method is appropriate for collecting muscle samples for the… Read more about this study
- Who is it for?
- Ages 60 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Cachexia
- What is being tested?
- Deuterated Water and Testosterone enanthate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 5 May 2014to 20 Mar 2015
- Phase
- Phase 1
- 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 60 to 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Males aged between 60-75 of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Ambulatory outside of home, stable chronic conditions allowed (if no clinically significant changes or major medication adjustments in previous 3 months) such as hypertension and/or dyslipidemia. Subjects must be able to satisfactorily complete each lower extremity 1-repetition maximum leg press assessment.
- Body weight >=50 kilogram and body mass index within the range 20 - 34 kilogram per square meter (inclusive)
- Renal clearance >= 45 milliliter per minute based on estimated Glomerular Filtration Rate (eGFR) calculated by the abbreviated MDRD equation, using serum creatinine and demographic data obtained at Screening.
- Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
- ALT, alkaline phosphatase and bilirubin =< 1.5x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Averaged corrected QT interval (QTc) values of 3 electrocardiograms separated by a 3-5 minute period: Bazett's QTc (QTcB) or Fridericia's QTc (QTcF) < 460 msec; or QTcB or QTcF < 480 msec in subjects with Partial Bundle Branch Block.
Who cannot join
- Subjects with a history of clinically significant endocrine, gastrointestinal, cardiovascular, neurological, haematological, immunological, renal, respiratory, vertigo, dizziness, prostate enlargement, or genitourinary abnormalities or diseases
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of muscular or neuromuscular disease such as multiple sclerosis, myasthenia gravis, muscular dystrophy, amyotrophic lateral sclerosis, stroke or transient ischemic attack
- Hospitalization in the past 6 months
- Current or recent use of ACE-inhibitors and/or systemic steroids
- Diabetes (Type 1, Type 2)
Show all 23Show fewer
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males. One drink is equivalent to 12 gram of alcohol: 12 ounces (360 milliliter [mL]) of beer, 5 ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled spirits.
- History of sensitivity to any of the local anaesthetics, study diagnostic reagents, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.
- History of bleeding disorder, including thrombocytopenia and other coagulopathies, or current use of anti-coagulants.
- A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening
- Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
- A positive pre-study drug/alcohol screen.
- A positive test for human immunodeficiency virus antibody.
- Electrolytes - Sodium more than +-5 milliequivalent per liter (mEq/L) outside the normal reference range, Potassium or Calcium more than 10% outside the normal reference range (<0.9 x lower limit of normal [LLN] or >1.1 x ULN)
- Metabolic - Glucose more than 10% outside the normal reference range (<0.9 x LLN or >1.1 x ULN) or Total Cholesterol > 240 milligram per deciliter
- Muscle - creatine phosphokinase >2.0 x ULN
- Hematology - Hemoglobin, White blood cells, Neutrophils, or Platelets more than 10% outside the normal reference range (<0.9 x LLN or >1.1 x ULN)
- A pro time/prothrombin time test (PT/PTT) outside the normal reference range for the assay.
- Prostate Specific Antigen (PSA) >=3.0 nanogram per milliliter
- Significant prostate enlargement upon clinical examination.
- Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first deuterated water (D2O) dosing day from the Run-in Phase in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than four new chemical entities within 12 months prior to the first D2O dosing day in the Run-in Phase.
Trial locations and contacts
1 site in 1 country.
United States1 site
GSK Investigational Site
Durham, North Carolina, 27705
About this study
Official title: A Pilot Study in Healthy Male Volunteers to Evaluate a Skeletal-Muscle Microbiopsy Technique for Suitability of Use With Dynamic Proteomic Measurement
This is a single-blind, randomized placebo-controlled, parallel study, where the study volunteers will be blinded to testosterone/placebo treatment. This study will test a relatively new, less invasive method for collecting muscle tissue to determine if this method is appropriate for collecting muscle samples for the assessment of the fractional synthetic rates (FSR) of muscle-derived proteins. This study will also investigate whether the FSR of proteins may serve as early biomarkers for muscle anabolism, a known anabolic agent (testosterone) will be administered to healthy, elderly male subjects over a 3 week period. The fractional synthetic rate of several muscle-derived proteins will be analyzed at Baseline and during the period of testosterone treatment using deuterium labelling of these proteins by the incorporation of deuterium from deuterated water (D2O).
- Conditions
- Cachexia
- Being tested
- Deuterated Water, Testosterone enanthate, Placebo to match testosterone enanthate
- Keywords
- muscle mass, dynamic proteomics, Duke University, Microbiopsy, D2O, testosterone, skeletal muscle
- Medical subject headings
- Cachexia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deuterated WaterDrug
D2O 70% will be supplied as clear liquid, provided in 50 millilitre (mL) unit dose vials; administered per orally.
Testosterone enanthateDrug
Testosterone enanthate 125mg injection will be supplied as colorless to pale yellow liquid; administered intramuscular (IM).
Placebo to match testosterone enanthateDrug
Placebo to match testosterone enanthate 0.625 mL injection will be supplied as greenish yellow, bright and clear oily liquid; administered intramuscular (IM).
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Run-in Phase: All participants will receive oral deuterated water (D2O) for 3 weeks prior to the Treatment Phase of the study. The participants will consume 50mL 70% D2O three times per day (TID) for 7 days, followed by a 50ml 70% D2O dose twice daily (BID) for the next 2 weeks. Treatment Phase: Subjects will receive testosterone matching placebo IM injection one per week and 50 mL 70% D2O dose BID for 3 weeks. Receives: Drug: Deuterated Water; Drug: Testosterone enanthate |
| Arm 2 | Placebo comparator | Run-in Phase: All participants will receive oral D2O for 3 weeks prior to the Treatment Phase of the study. The participants will consume 50 mL 70% D2O TID for 7 days, followed by a 50mL 70% D2O dose BID for the next 2 weeks. Treatment Phase: Subjects will receive testosterone IM injection one per week and 50 mL 70% D2O dose BID for 3 weeks Receives: Drug: Deuterated Water; Drug: Placebo to match testosterone enanthate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline in muscle derived protein synthesis rate
Muscle protein synthesis will be assessed by measuring the fractional synthetic rate of muscle-derived proteins in both muscle biopsy samples and in blood after subjects have ingested deuterated water. The FSR of several muscle-derived proteins will be analyzed at baseline and during the period of testosterone treatment using deuterium labelling of these proteins by the incorporation of deuterium from D2O.
Measured: Baseline and Day 21
Secondary outcomes (4)
Change from Baseline in lower extremity strength using the 1-repetition maximum (1-RM) leg strength, FSRs from muscle proteins derived from muscle biopsies and serum samples
Lower extremity strength will be measured as the 1-RM on a leg press device. Strength will be measured at baseline (Day 1, prior to start of testosterone) and at study end (Day 21). The FSR of several muscle-derived proteins will be analyzed at Baseline and during the period in both muscle biopsy samples and in blood after subjects have ingested deuterated water.
Measured: Baseline, Day 7, 14, and 21
Changes in FSR in muscle and serum derived muscle proteins
The FSR of several muscle-derived proteins will be analyzed at Baseline and during the period in both muscle biopsy samples and in blood after subjects have ingested deuterated water.
Measured: Baseline, Day 7, 14, and 21
Number of biopsy samples required to obtain desired collection weight
Measured: Baseline, Day 7, 14, and 21
Number of participants with biopsy-related adverse events
Measured: Upto Week 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2013 (estimated)
- Study start5 May 2014
- Primary completion20 Mar 2015
- Study completion20 Mar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CachexiaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01962454
- Sponsor's protocol ID
- 200030
- Status last verified
- May 2017
- First submitted
- 10 Oct 2013
- Last updated
- 9 May 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study in Healthy Male Volunteers to Evaluate a Skeletal-Muscle Microbiopsy Technique for Suitability of Use With Dynamic Proteomic Measurement
- ClinicalTrials.gov ID
- NCT01962454
- Acronym / sponsor ID
- 200030
- Conditions
- Cachexia
- Keywords
- muscle mass, dynamic proteomics, Duke University, Microbiopsy, D2O, testosterone, skeletal muscle
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 5 May 2014 (actual)
- Primary completion
- 20 Mar 2015 (actual)
- Study completion
- 20 Mar 2015 (actual)
- First posted
- 14 Oct 2013 (estimated)
- 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.
This is a single-blind, randomized placebo-controlled, parallel study, where the study volunteers will be blinded to testosterone/placebo treatment. This study will test a relatively new, less invasive method for collecting muscle tissue to determine if this method is appropriate for collecting muscle samples for the assessment of the fractional synthetic rates (FSR) of muscle-derived proteins. This study will also investigate whether the FSR of proteins may serve as early biomarkers for muscle anabolism, a known anabolic agent (testosterone) will be administered to healthy, elderly male subjects over a 3 week period. The fractional synthetic rate of several muscle-derived proteins will be analyzed at Baseline and during the period of testosterone treatment using deuterium labelling of these proteins by the incorporation of deuterium from deuterated water (D2O).
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Deuterated Water, Drug: Testosterone enanthateRun-in Phase: All participants will receive oral deuterated water (D2O) for 3 weeks prior to the Treatment Phase of the study. The participants will consume 50mL 70% D2O three times per day (TID) for 7 days, followed by a 50ml 70% D2O dose twice daily (BID) for the next 2 weeks. Treatment Phase: Subjects will receive testosterone matching placebo IM injection one per week and 50 mL 70% D2O dose BID for 3 weeks. |
| Arm 2 | Placebo comparator | Drug: Deuterated Water, Drug: Placebo to match testosterone enanthateRun-in Phase: All participants will receive oral D2O for 3 weeks prior to the Treatment Phase of the study. The participants will consume 50 mL 70% D2O TID for 7 days, followed by a 50mL 70% D2O dose BID for the next 2 weeks. Treatment Phase: Subjects will receive testosterone IM injection one per week and 50 mL 70% D2O dose BID for 3 weeks |
Who may qualify
- Ages
- 60 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males aged between 60-75 of age inclusive, at the time of signing the informed consent.
- Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameter(s) which is/are not specifically listed in the inclusion or exclusion criteria, outside the reference range for the population being studied may be included only if the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
- Ambulatory outside of home, stable chronic conditions allowed (if no clinically significant changes or major medication adjustments in previous 3 months) such as hypertension and/or dyslipidemia. Subjects must be able to satisfactorily complete each lower extremity 1-repetition maximum leg press assessment.
- Body weight >=50 kilogram and body mass index within the range 20 - 34 kilogram per square meter (inclusive)
- Renal clearance >= 45 milliliter per minute based on estimated Glomerular Filtration Rate (eGFR) calculated by the abbreviated MDRD equation, using serum creatinine and demographic data obtained at Screening.
Key exclusion criteria (23 listed)
- Subjects with a history of clinically significant endocrine, gastrointestinal, cardiovascular, neurological, haematological, immunological, renal, respiratory, vertigo, dizziness, prostate enlargement, or genitourinary abnormalities or diseases
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- History of muscular or neuromuscular disease such as multiple sclerosis, myasthenia gravis, muscular dystrophy, amyotrophic lateral sclerosis, stroke or transient ischemic attack
- Hospitalization in the past 6 months
- Current or recent use of ACE-inhibitors and/or systemic steroids
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 |
|---|---|---|
| Deuterated WaterD2O 70% will be supplied as clear liquid, provided in 50 millilitre (mL) unit dose vials; administered per orally. | Drug | Arm 1, Arm 2 |
| Testosterone enanthateTestosterone enanthate 125mg injection will be supplied as colorless to pale yellow liquid; administered intramuscular (IM). | Drug | Arm 1 |
| Placebo to match testosterone enanthatePlacebo to match testosterone enanthate 0.625 mL injection will be supplied as greenish yellow, bright and clear oily liquid; administered intramuscular (IM). | Drug | Arm 2 |
Primary outcome
Change from Baseline in muscle derived protein synthesis rate
Time frame: Baseline and Day 21
Muscle protein synthesis will be assessed by measuring the fractional synthetic rate of muscle-derived proteins in both muscle biopsy samples and in blood after subjects have ingested deuterated water. The FSR of several muscle-derived proteins will be analyzed at baseline and during the period of testosterone treatment using deuterium labelling of these proteins by the incorporation of deuterium from D2O.
4 secondary outcomes
Change from Baseline in lower extremity strength using the 1-repetition maximum (1-RM) leg strength, FSRs from muscle proteins derived from muscle biopsies and serum samples
Time frame: Baseline, Day 7, 14, and 21
Changes in FSR in muscle and serum derived muscle proteins
Time frame: Baseline, Day 7, 14, and 21
Number of biopsy samples required to obtain desired collection weight
Time frame: Baseline, Day 7, 14, and 21
Number of participants with biopsy-related adverse events
Time frame: Upto Week 7
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 9 May 2017.
- Results for study 200030 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Deuterated Water and Testosterone enanthate in people with Cachexia, run by GlaxoSmithKline 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 8 inclusion and 23 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 9 May 2017. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change from Baseline in muscle derived protein synthesis rate (time frame: Baseline and Day 21). 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 9 May 2017.