AgingNCT02472340
Mitophagy and Autophagy in Elderly Subjects
An observational study of Aging and Frailty, run by Amazentis SA at 1 site in Netherlands.
Trial summary
In recent years, evidence has shown that mitochondrial dysfunction plays an important role in the development of age-related muscle decline that may lead to frailty. During aging, there is a progressive reduction in the cell's capacity to eliminate its dysfunctional elements by autophagy, as evidenced by the… Read more about this study
- Who is it for?
- Ages 61 to 85 yearsHealthy volunteers can take part
- What is being tested?
- Muscle Biopsy
- Type of treatment
- Surgery or procedure
- How many people
- 22 participants
- Where
- 1 siteNetherlands
- Study dates
- Jun 2015to Jul 2016
- Phase
- Observational
- 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 61 to 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: * 10 active, healthy elderly, >61 years of age * 10 sedentary, pre-frail elderly, >61 years of age
Who may be able to join
- for Active, Healthy subjects:
- >61 years of age, inclusive.
- Healthy male subjects. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, haematology, blood chemistry, and urinalysis.
- Body mass index (BMI) between 15 and 32 kg/m2, inclusive.
- Able to participate and willing to give written informed consent and to comply with the study restrictions.
- Category 2 or 3 as assessed by the International Physical Activity Questionnaires (IPAQ). Activity level is ≥ 600 MET (metabolic equivalent unit) - minutes per week.
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- Normal physical performance: normal gait speed, i.e. a walking ≥ 0.8 m/s in the 4-m walking test.
- Normal muscle mass: normal skeletal muscle mass index (SMI), measured by Bioimpedance analysis (BIA, ≥ 10.75 kg/m2).
- Normal muscle strength: handgrip strength (measured with the Jamar dynamometer) of ≥ 30 kg.
- for Sedentary, Pre-frail subjects:
- Sedentary, pre-frail males. Pre-frailty is defined as fulfilling to at least two out of the following three criteria: low physical performance (low gait speed, i.e. a walking speed below 0.8 m/s in the 4-m walking test), low muscle mass (a low skeletal muscle mass index (SMI), measured by Bioimpedance analysis (BIA, < 10.75 kg/m2)) and/or low muscle strength: handgrip strength (measured with the Jamar dynamometer) of < 30 kg. Sedentary behaviour is defined as having an activity category of 1 as assessed by the International Physical Activity Questionnaires (IPAQ) (Activity level is ≥ 600 MET (metabolic equivalent unit) - minutes per week).
- Body mass index (BMI) between 15 and 32 kg/m2, inclusive.
- Able to participate and willing to give written informed consent and to comply with the study restrictions.
- >61 years of age, inclusive.
Who cannot join
- for Active, Healthy subjects:
- Presence of any contraindication to have MRI scans performed (e.g. pacemaker, intracranial clips etc.).
- Having diabetes mellitus or lower extremity peripheral vascular disease, as these conditions may interfere with interpretation of the dynamic 31P-MRS and NIRS of the lower extremity.
- Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year.
- A history (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol).
- Smoking within 3 months prior to screening and inability to refrain from smoking during the course of the study (from screening to End-of-Study [EOS]).
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- A history or presence of allergy to 5-aminolevulinic acid or porphyrins.
- A history or presence of allergy to lidocaine.
- Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
- Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening.
- Unwillingness or inability to refrain from consuming alcohol within 48 hours before each visit until the end of that visit.
- Unwillingness or inability to refrain from consuming 8 or more units of xanthine containing beverages and foods per day during the entire study.
- Unwillingness or inability to refrain from consuming the following supplements: L-carnitine, creatine, Q10, vitamin A, niacin, folic acid, vitamin C, vitamin E and probiotic- foods and supplements at least two weeks before study enrolment.
- Unwillingness or inability to have a muscle biopsy performed.
- For Sedentary, Pre-frail subjects
- Presence of any contraindication to have MRI scans performed (e.g. pacemaker, intracranial clips etc.).
- Having diabetes mellitus or lower extremity peripheral vascular disease, as these conditions may interfere with interpretation of the dynamic 31P-MRS and NIRS of the lower extremity.
- Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year.
- A history (within 3 months of screening) of alcohol consumption exceeding 2 standard drinks per day on average (1 standard drink = 10 grams of alcohol).
- Smoking within 3 months prior to screening and inability to refrain from smoking during the course of the study (from screening to EOS).
- A history or presence of allergy to 5-aminolevulinic acid or porphyrins.
- A history or presence of allergy to lidocaine.
- Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus antibody (HIV Ab) at screening.
- Loss or donation of blood over 500 mL within three months (males) or four months (females) prior to screening.
- Unwillingness or inability to refrain from consuming alcohol within 48 hours before each visit until the end of that visit.
- Unwillingness or inability to refrain from consuming 8 or more units of xanthine containing beverages and foods per day during the entire study.
- Unwillingness or inability to refrain from consuming the following supplements: L-carnitine, creatine, Q10, vitamin A, niacin, folic acid, vitamin C, vitamin E and probiotic- foods and supplements at least two weeks before study enrolment.
- Unwillingness or inability to have a muscle biopsy performed.
- Underlying chronic disease, which, in the opinion of the investigator would interfere with study participation or the validity of the measurements.
- Unintentional weight loss ≤5% of usual body weight during the last 6 months.
- Anorexia or anorexia-related symptoms
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment and Reproducibility of Mitochondrial Function and Mitophagy Measurements in Human Muscle Tissue of Active and Pre Frail Elderly Males
In recent years, evidence has shown that mitochondrial dysfunction plays an important role in the development of age-related muscle decline that may lead to frailty.
During aging, there is a progressive reduction in the cell's capacity to eliminate its dysfunctional elements by autophagy, as evidenced by the accumulation of oxidative damage and mutations in mitochondria and by the decrease in autophagic flux. In fact, it has been demonstrated that dysfunctional mitochondria can be specifically targeted for elimination by autophagy, a process that has been termed mitophagy.
Read more
A major challenge in the clinic today is in the lack of validated tools, including biomarkers, to assess the decline in mitochondrial health associated with an impairment in muscle function. In the present study, the investigators will employ a battery of established and exploratory tests (clinical, physiological and molecular) to assess in vivo mitochondrial function and more specifically, the levels of mitophagy and autophagy, in the muscle of healthy and pre-frail elderly.
It is anticipated that the results of this study will facilitate the rapid translation of interventions targeting mitophagy and autophagy for the improvement of muscle function.
- Being tested
- Muscle Biopsy
- Medical subject headings
- Frailty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Muscle BiopsyProcedure or surgery
Muscle Biopsy
| Study group | Role | What they receive |
|---|---|---|
| Sedentary, Pre-frail | 10 sedentary, pre-frail elderly, >61 year of age Receives: Procedure: Muscle Biopsy | |
| Active, Healthy | 10 Active, healthy elderly, >61 years of age Receives: Procedure: Muscle Biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Gene and protein expression for autophagy and mitophagy biomarkers in muscle tissue
Measured: 9 months
Secondary outcomes (8)
PCr recovery time (in seconds) measured by 31P-MRS (31-Phosphorus Magnetic Resonance Spectroscopy).
Measured: 9 months
mVO2 (in ml/min/100 ml) in muscle measured by NIRS (Near-infrared Spectroscopy)
Measured: 9 months
MitoPO2 (in mmHg) in the skin measured by PpIX-TSLT (Protoporphyrin IX - Triplet State Lifetime Technique).
Measured: 9 months
Hand grip strength (in kg) measured by the Jamar dynamometer.
Measured: 9 months
Peak muscle force of quadriceps measured by handheld dynamometry
Measured: 9 months
Postural stability (in mm sway) measured by body sway
Measured: 9 months
Level of activity, using the Vital Connect HealthPatch accelerometer
Measured: 9 months
Short physical performance battery (SPPB) test.
Measured: 9 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2015 (estimated)
- Study startJun 2015
- Primary completionApr 2016
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AgingStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amazentis SA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Centre for Human Drug Research, Netherlands
- Responsible party
- Sponsor
- Investigators
- Geert Jan Groeneveld, MD, PhD, Principal investigator, CHDRAnurag Singh, MD, PhD, Study director, Amazentis SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02472340
- Sponsor's protocol ID
- CHDR1510
- Other IDs
- 15.01.AMZ
- Status last verified
- Mar 2016
- First submitted
- 9 Jun 2015
- Last updated
- 1 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment and Reproducibility of Mitochondrial Function and Mitophagy Measurements in Human Muscle Tissue of Active and Pre Frail Elderly Males
- ClinicalTrials.gov ID
- NCT02472340
- Acronym / sponsor ID
- CHDR1510
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Amazentis SAIndustry (pharma, biotech, devices)
- Collaborators
- Centre for Human Drug Research, Netherlands
- Study start
- Jun 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 15 Jun 2015 (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.
In recent years, evidence has shown that mitochondrial dysfunction plays an important role in the development of age-related muscle decline that may lead to frailty.
During aging, there is a progressive reduction in the cell's capacity to eliminate its dysfunctional elements by autophagy, as evidenced by the accumulation of oxidative damage and mutations in mitochondria and by the decrease in autophagic flux. In fact, it has been demonstrated that dysfunctional mitochondria can be specifically targeted for elimination by autophagy, a process that has been termed mitophagy.
A major challenge in the clinic today is in the lack of validated tools, including biomarkers, to assess the decline in mitochondrial health associated with an impairment in muscle function. In the present study, the investigators will employ a battery of established and exploratory tests (clinical, physiological and molecular) to assess in vivo mitochondrial function and more specifically, the levels of mitophagy and autophagy, in the muscle of healthy and pre-frail elderly.
It is anticipated that the results of this study will facilitate the rapid translation of interventions targeting mitophagy and autophagy for the improvement of muscle function.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sedentary, Pre-frail | – | Procedure: Muscle Biopsy10 sedentary, pre-frail elderly, >61 year of age |
| Active, Healthy | – | Procedure: Muscle Biopsy10 Active, healthy elderly, >61 years of age |
Who may qualify
- Ages
- 61 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- * 10 active, healthy elderly, >61 years of age * 10 sedentary, pre-frail elderly, >61 years of age
Key inclusion criteria (14 listed)
- for Active, Healthy subjects:
- Sedentary, pre-frail males. Pre-frailty is defined as fulfilling to at least two out of the following three criteria: low physical performance (low gait speed, i.e. a walking speed below 0.8 m/s in the 4-m walking test), low muscle mass (a low skeletal muscle mass index (SMI), measured by Bioimpedance analysis (BIA, < 10.75 kg/m2)) and/or low muscle strength: handgrip strength (measured with the Jamar dynamometer) of < 30 kg. Sedentary behaviour is defined as having an activity category of 1 as assessed by the International Physical Activity Questionnaires (IPAQ) (Activity level is ≥ 600 MET (metabolic equivalent unit) - minutes per week).
- Body mass index (BMI) between 15 and 32 kg/m2, inclusive.
- Able to participate and willing to give written informed consent and to comply with the study restrictions.
- >61 years of age, inclusive.
Key exclusion criteria (31 listed)
- for Active, Healthy subjects:
- For Sedentary, Pre-frail subjects
- Presence of any contraindication to have MRI scans performed (e.g. pacemaker, intracranial clips etc.).
- Having diabetes mellitus or lower extremity peripheral vascular disease, as these conditions may interfere with interpretation of the dynamic 31P-MRS and NIRS of the lower extremity.
- Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year.
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 |
|---|---|---|
| Muscle BiopsyMuscle Biopsy | Procedure or surgery | Active, Healthy, Sedentary, Pre-frail |
Primary outcome
Gene and protein expression for autophagy and mitophagy biomarkers in muscle tissue
Time frame: 9 months
8 secondary outcomes
PCr recovery time (in seconds) measured by 31P-MRS (31-Phosphorus Magnetic Resonance Spectroscopy).
Time frame: 9 months
mVO2 (in ml/min/100 ml) in muscle measured by NIRS (Near-infrared Spectroscopy)
Time frame: 9 months
MitoPO2 (in mmHg) in the skin measured by PpIX-TSLT (Protoporphyrin IX - Triplet State Lifetime Technique).
Time frame: 9 months
Hand grip strength (in kg) measured by the Jamar dynamometer.
Time frame: 9 months
Peak muscle force of quadriceps measured by handheld dynamometry
Time frame: 9 months
Postural stability (in mm sway) measured by body sway
Time frame: 9 months
Level of activity, using the Vital Connect HealthPatch accelerometer
Time frame: 9 months
Short physical performance battery (SPPB) test.
Time frame: 9 months
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 1 Aug 2016.
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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.
Geert Jan Groeneveld, MD, PhD principal investigator
CHDR
Anurag Singh, MD, PhD study director
Amazentis SA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aging and Frailty, run by Amazentis SA at 1 site in Netherlands.
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 14 inclusion and 31 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 1 Aug 2016. 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 Netherlands. 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. 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?
Gene and protein expression for autophagy and mitophagy biomarkers in muscle tissue (time frame: 9 months). 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 1 Aug 2016.