Last updated: 11/07/2018 11:28:26
Estimation of Skeletal Muscle Mass with Deuterium Labeled d3 Creatine in Subjects with Chronic Disease
Clinicaltrials.gov ID
Not applicable
EudraCT ID
Not applicable
EU CT Number
Not applicable
Trial status
Other
Other
Trial overview
Official title: Estimation of Skeletal Muscle Mass with Deuterium Labeled d3 Creatine in Subjects with Chronic Disease
Trial description: This is a single centre, open-label study in elderly and postmenopausal subjects and subjects with congestive heart failure (CHF) or chronic obstructive lung disease (COPD). Subjects will be given a single dose of Deuterium Labeled (D3) creatine 30 milligram (mg) on Day 1, followed by collection of urine and serum for 4 days. The duration of the study is 5 days treatment period and 10 to 14 days follow-up period. Subjects who complete treatment period 1 may be re-dosed approximately 3 months after completion of first dosing session.This study forms part of the SPRINT-T project. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking (www.imieuropa.eu) under grant agreement n° 115621, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7 / 2007-2013) and EFPIA companies’ in kind contribution.
Primary purpose:
Diagnostic
Trial design:
Single Group Assignment
Masking:
None (Open Label)
Allocation:
N\A
Primary outcomes:
Muscle mass as calculated by d3 creatine dilution method, DEXA and MRI
Timeframe: 4 days
Secondary outcomes:
Plasma d3 creatinine PK
Timeframe: Pre-dose , 0.5, 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 48, and 72 hrs post-dose
Estimates of d3 creatine, d3 creatinine, creatine, and creatinine levels by LCMS in urine for each urine collection interval
Timeframe: 22 days
Creatine pool size
Timeframe: 22 days
Cumulative % of d3 creatine dose excreted in urine
Timeframe: 22 days
Estimated time of d3 creatine, d3 creatinine, creatine, and creatinine enrichment in urine
Timeframe: 22 days
Levels of creatinine and creatine in urine
Timeframe: 22 days
Interventions:
Enrollment:
42
Primary completion date:
Not applicable
Observational study model:
Cohort
Time perspective:
Other
Clinical publications:
Richard V Clark, Ann C Walker, Ram R Miller, Robin L O’Connor Semmes, Eric Ravussin, William T Cefalu. Creatine (methyl-d3) dilution in urine for estimation of total body skeletal muscle mass—accuracy and variability vs. MRI and DXA. J Appl Physiol. 2018;124(1):1-9.
Medical condition
Atrophy, Muscular
Product
CCI21130
Collaborators
None
Study date(s)
September 2013 to November 2014
Type
Interventional
Phase
1
Participation criteria
Sex
Female & Male
Age
50 - 85 Year
Accepts healthy volunteers
yes
- Three cohorts of males and postmenopausal women:
- (a) Healthy Elderly age 65-85 yrs (years) at the time of signing the informed consent, Healthy for age, functional outside of home, stable chronic conditions allowed (if no clinically significant changes or major medication adjustments in previous 3 months) such as hypertension, dyslipidemia, type 2 diabetes mellitus (T2DM) (glycosylated haemoglobin [A1C] <7% and no insulin, Cardiovascular disease (CVD);
- Current or chronic history of liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Any positive test for human immunodeficiency virus (HIV) antibody or Hepatitis B surface antigen, or for Hepatitis C antibody within 3 months of screening.
Inclusion and exclusion criteria
Inclusion criteria:
- Three cohorts of males and postmenopausal women: (a) Healthy Elderly age 65-85 yrs (years) at the time of signing the informed consent, Healthy for age, functional outside of home, stable chronic conditions allowed (if no clinically significant changes or major medication adjustments in previous 3 months) such as hypertension, dyslipidemia, type 2 diabetes mellitus (T2DM) (glycosylated haemoglobin [A1C] <7% and no insulin, Cardiovascular disease (CVD); (b) CHF: Age of 50 to 85 yrs at the time of signing the informed consent, with a confirmed diagnosis of heart failure (HF) with The New York Heart Association (NYHA) Functional Classification NYHA functional class II or III, and clinically stabile without hospital admission for HF in the previous 3 months; c) chronic obstructive pulmonary disease (COPD): Age of 50 to 85 yrs at the time of signing the informed consent, with a confirmed diagnosis of COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stage 3 or 4) with forced expiratory volume in 1 second (FEV1) <70% of predicted and with <10% response to beta-agonist. Based on discussion with the medical monitor, patients must be clinically stable and not suffering from a recent respiratory tract infection or disease exacerbation within 2 months
- Body mass index (BMI) within the range 18-34 kilogram/meter square (kg/m^2) (inclusive)
- Ambulatory outside of home, stable chronic conditions allowed (if no clinically significant changes or major medication adjustments in previous 3 months) such as hypertension, dyslipidemia, type II diabetes mellitus (T2DM) (A1C <9% for CHF and COPD)
- Renal clearance >=45 millilitres/ minute (mL/min) based on estimated Glomerular Filtration Rate (eGFR) calculated by the abbreviated Modification of Diet in Renal Disease (MDRD) equation, using serum creatinine (SCR) 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
Exclusion criteria:
- Current or chronic history of liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Any positive test for human immunodeficiency virus (HIV) antibody or Hepatitis B surface antigen, or for Hepatitis C antibody within 3 months of screening.
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase >=1.5x upper limit of normal (ULN) and bilirubin >=1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
- Confirmed QT corrected using Bazett's QTcB or QT corrected using Fridericia's formula (QTcF) >480 milliseconds (msec); or QTc >500 msec in subjects with Bundle Branch Block.
- Subjects currently on Atkins or high animal protein diets (e.g. >120 gram [g]/day of protein for men; >80 g/day protein for women) or low animal protein diets (e.g vegetarians or vegans).
- Malignances within prior 12 months, except for surgically excised skin tumors
- Additional disease specific criteria: Patients are excluded if they have had unstable angina or acute myocardial infarction in the past 3 months, history of severe liver or renal diseases, uncontrolled hypertension, erythrocytosis (hematocrit _50%); chronic hypoxemia at rest requiring continuous oxygen support (Pao2 <7.3 kilopascal (kPa) / 55 millimeters of mercury [mmHg]),
- Systolic blood pressure greater than 160 mmHg, or diastolic blood pressure greater than 100 mmHg at Screening.
- History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of >14 drinks for males or >7 drinks for females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
- Prohibited medications: no systemic glucocorticoids (inhaled glucocorticoids are allowed), testosterone, growth hormone or cimetidine. Insulin use may be allowed with approval from the medical monitor based on overall glycemic control of subject.
- Use of creatine supplements within 1 months of dosing
- Use vitamins, herbal and dietary supplements, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
- Medications taken for CHF or COPD should have been stable for the prior 30 days and for the duration of this study.
- History of sensitivity to heparin or heparin-induced thrombocytopenia.
- A positive pre-study drug/alcohol screen.
Trial location(s)
This study does not involve prospective enrollment of participants.
Study documents
Scientific result summary
Available language(s): English
Protocol
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Refer to study documents
Recruitment status
Other
Actual primary completion date
Not applicable
Actual study completion date
2014-14-11
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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