mitochondriele dysfunctie defect of the powerhouse of the cell Mitochondrial dysfunction
Conditions
Interventions
None listed
Sponsors
Amazentis SA
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Inclusion criteria for active, healthy subjects;1. 61 years of age or older, inclusive. 2. Healthy male or female 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 35 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, for males >= 10.75 kg/m2, for females >= 6.75 kg/m2). 8. Normal muscle strength: handgrip strength (measured with the Jamar dynamometer) of >= 30 kg for males and >= 20 kg for females.;Inclusion criteria 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, for males
Exclusion criteria
Exclusion criteria: 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 3 standard drinks per day on average (1 standard drink = 10 grams of alcohol). 5. Inability to refrain from smoking more than half a pack of cigarettes (or similar for other tobacco products) per day 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.;Exclusion criteria 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 3 standard drinks per day on average (1 standard drink = 10 grams of alcohol). 5. Inability to refrain from smoking more than half a pack of cigarettes (or similar for other tobacco products) per day 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 probio
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the level of mitophagy and autophagy in muscle biopsy tissue of active healthy elderly subjects and sedentary pre-frail elderly subjects using 1) gene expression and 2) protein expression analysis for candidate genes linked to mitophagy and autophagy biological process. | — |
Secondary
| Measure | Time frame |
|---|---|
| - PCr recovery time (in seconds) measured by 31P-MRS. - Ratio of mtDNA to nuDNA measured by qPCR. - Activity of citrate synthase and respiratory complexes measured by assay in muscle tissue. - mVO2 (in ml/min/100 ml) in muscle measured by NIRS. - MitoPO2 (in mmHg) in the skin measured by PpIX-TSLT. - Hand grip strength (in kg) measured by the Jamar dynamometer. - Strength during maximum voluntary isometric contraction of the quadriceps (in kg). - Postural stability (in cm sway) measured by body sway. - Ability to maintain standing balance (yes/no), as part of the Short Physical Performance Battery (SPPB). - Level of activity, using the Vital Connect Healthpatch accelerometer. - 4-meter walking speed (in m/s), as part of the SPPB. - Sit-to-stand transfer (in s), as part of the SPPB. | — |
Countries
Netherlands
Outcome results
None listed