Mitophagy and Autophagy in Elderly Subjects

• Register: ClinicalTrials.gov
• Last refreshed on: 8 August 2016
• Main ID: NCT02472340
• Date of registration: 09/06/2015
• Prospective Registration: No
• Primary sponsor: Amazentis SA
• Public title: Mitophagy and Autophagy in Elderly Subjects
• Scientific title: Assessment and Reproducibility of Mitochondrial Function and Mitophagy Measurements in Human Muscle Tissue of Active and Pre Frail Elderly Males
• Date of first enrolment: June 2015
• Target sample size: 22
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02472340
• Study type: Observational
• Study design: Observational Model: Cohort, Time Perspective: Cross-Sectional
• Phase: N/A

Countries of recruitment

Netherlands

Contacts

• Name: Anurag Singh, MD, PhD
• Affiliation: Amazentis SA

• Name: Geert Jan Groeneveld, MD, PhD
• Affiliation: CHDR

Key inclusion & exclusion criteria

Inclusion Criteria:

- for Active, Healthy subjects:

1. >61 years of age, inclusive.

2. 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.

3. Body mass index (BMI) between 15 and 32 kg/m2, inclusive.

4. Able to participate and willing to give written informed consent and to comply
with the study restrictions.

5. Category 2 or 3 as assessed by the International Physical Activity
Questionnaires (IPAQ). Activity level is = 600 MET (metabolic equivalent unit) -
minutes per week.

6. Normal physical performance: normal gait speed, i.e. a walking = 0.8 m/s in the
4-m walking test.

7. Normal muscle mass: normal skeletal muscle mass index (SMI), measured by
Bioimpedance analysis (BIA, = 10.75 kg/m2).

8. Normal muscle strength: handgrip strength (measured with the Jamar dynamometer)
of = 30 kg.

for Sedentary, Pre-frail subjects:

1. 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).

2. Body mass index (BMI) between 15 and 32 kg/m2, inclusive.

3. Able to participate and willing to give written informed consent and to comply with
the study restrictions.

4. >61 years of age, inclusive.

Exclusion Criteria:

- for Active, Healthy subjects:

1. Presence of any contraindication to have MRI scans performed (e.g. pacemaker,
intracranial clips etc.).

2. 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.

3. Participation in a clinical trial within 90 days of screening or more than 4
times in the previous year.

4. 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).

5. 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]).

6. A history or presence of allergy to 5-aminolevulinic acid or porphyrins.

7. A history or presence of allergy to lidocaine.

8. Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or
human immunodeficiency virus antibody (HIV Ab) at screening.

9. Loss or donation of blood over 500 mL within three months (males) or four months
(females) prior to screening.

10. Unwillingness or inability to refrain from consuming alcohol within 48 hours
before each visit until the end of that visit.

11. Unwillingness or inability to refrain from consuming 8 or more units of xanthine
containing beverages and foods per day during the entire study.

12. 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.

13. Unwillingness or inability to have a muscle biopsy performed.

For Sedentary, Pre-frail subjects

1. Presence of any contraindication to have MRI scans performed (e.g. pacemaker,
intracranial clips etc.).

2. 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.

3. Participation in a clinical trial within 90 days of screening or more than 4 times in
the previous year.

4. 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).

5. Smoking within 3 months prior to screening and inability to refrain from smoking
during the course of the study (from screening to EOS).

6. A history or presence of allergy to 5-aminolevulinic acid or porphyrins.

7. A history or presence of allergy to lidocaine.

8. Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human
immunodeficiency virus antibody (HIV Ab) at screening.

9. Loss or donation of blood over 500 mL within three months (males) or four months
(females) prior to screening.

10. Unwillingness or inability to refrain from consuming alcohol within 48 hours before
each visit until the end of that visit.

11. Unwillingness or inability to refrain from consuming 8 or more units of xanthine
containing beverages and foods per day during the entire study.

12. 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.

13. Unwillingness or inability to have a muscle biopsy performed.

14. Underlying chronic disease, which, in the opinion of the investigator would interfere
with study participation or the validity of the measurements.

15. Unintentional weight loss =5% of usual body weight during the last 6 months.

16. Anorexia or anorexia-related symptoms



Age minimum: 61 Years
Age maximum: 85 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Mitophagy

Aging

Frailty

Intervention(s)

Procedure: Muscle Biopsy

Primary Outcome(s)

Gene and protein expression for autophagy and mitophagy biomarkers in muscle tissue [Time Frame: 9 months]

Secondary Outcome(s)

MitoPO2 (in mmHg) in the skin measured by PpIX-TSLT (Protoporphyrin IX - Triplet State Lifetime Technique). [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]

mVO2 (in ml/min/100 ml) in muscle measured by NIRS (Near-infrared Spectroscopy) [Time Frame: 9 months]

Short physical performance battery (SPPB) test. [Time Frame: 9 months]

Hand grip strength (in kg) measured by the Jamar dynamometer. [Time Frame: 9 months]

PCr recovery time (in seconds) measured by 31P-MRS (31-Phosphorus Magnetic Resonance Spectroscopy). [Time Frame: 9 months]

Level of activity, using the Vital Connect HealthPatch accelerometer [Time Frame: 9 months]

Secondary ID(s)

15.01.AMZ

CHDR1510

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Centre for Human Drug Research, Netherlands