Trial Outcomes & Findings for Mitochondrial Stress, Brain Imaging, and Epigenetics (NCT NCT04831424)
NCT ID: NCT04831424
Last Updated: 2025-05-20
Results Overview
This is designed to measure cortisol reactivity to the trier social stress test (TSST), quantified from salivary cortisol (LC-MS) over an 8-timepoints timecourse. The elevation will be measured as the area under the curve (AUC) for the cortisol time course.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
110 participants
Primary outcome timeframe
Day 1 post challenge (approximately 2 hours)
Results posted on
2025-05-20
Participant Flow
Participant milestones
| Measure |
Healthy Controls
No diagnosis of mitochondrial disease
|
Mutation
Participants carrying the m.3243A\>G point mutation, without a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
Deletion
Participants carrying a single, large-scale mtDNA deletion
|
Mutation With MELAS
Participants carrying the m.3243A\>G point mutation, with a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
70
|
20
|
15
|
5
|
|
Overall Study
COMPLETED
|
70
|
20
|
15
|
5
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Mitochondrial Stress, Brain Imaging, and Epigenetics
Baseline characteristics by cohort
| Measure |
Healthy Controls
n=70 Participants
No diagnosis of mitochondrial disease
|
Mutation
n=20 Participants
Participants carrying the m.3243A\>G point mutation, without a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
Deletion
n=15 Participants
Participants carrying a single, large-scale mtDNA deletion
|
Mutation With MELAS
n=5 Participants
Participants carrying the m.3243A\>G point mutation, with a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
Total
n=110 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
37.1 years
STANDARD_DEVIATION 10.6 • n=99 Participants
|
34.4 years
STANDARD_DEVIATION 11.2 • n=107 Participants
|
43.1 years
STANDARD_DEVIATION 9.8 • n=206 Participants
|
39.2 years
STANDARD_DEVIATION 7.6 • n=7 Participants
|
37.5 years
STANDARD_DEVIATION 10.7 • n=31 Participants
|
|
Sex: Female, Male
Female
|
48 Participants
n=99 Participants
|
15 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
2 Participants
n=7 Participants
|
76 Participants
n=31 Participants
|
|
Sex: Female, Male
Male
|
22 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
3 Participants
n=7 Participants
|
34 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
10 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
62 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
14 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
100 Participants
n=31 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Asian
|
5 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
6 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Black or African American
|
10 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
11 Participants
n=31 Participants
|
|
Race (NIH/OMB)
White
|
47 Participants
n=99 Participants
|
18 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
5 Participants
n=7 Participants
|
82 Participants
n=31 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=31 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
0 Participants
n=7 Participants
|
7 Participants
n=31 Participants
|
|
Region of Enrollment
United States
|
70 participants
n=99 Participants
|
20 participants
n=107 Participants
|
15 participants
n=206 Participants
|
5 participants
n=7 Participants
|
110 participants
n=31 Participants
|
PRIMARY outcome
Timeframe: Day 1 post challenge (approximately 2 hours)This is designed to measure cortisol reactivity to the trier social stress test (TSST), quantified from salivary cortisol (LC-MS) over an 8-timepoints timecourse. The elevation will be measured as the area under the curve (AUC) for the cortisol time course.
Outcome measures
| Measure |
Healthy Controls
n=70 Participants
No diagnosis of mitochondrial disease
|
Mutation
n=20 Participants
Participants carrying the m.3243A\>G point mutation, without a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
Deletion
n=15 Participants
Participants carrying a single, large-scale mtDNA deletion
|
Mutation With MELAS
n=5 Participants
Participants carrying the m.3243A\>G point mutation, with a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
|---|---|---|---|---|
|
Average TSST-induced Elevation in Cortisol
|
37.44 ng*min/mL
Standard Deviation 114.60
|
33.86 ng*min/mL
Standard Deviation 54.46
|
42.83 ng*min/mL
Standard Deviation 35.83
|
45.42 ng*min/mL
Standard Deviation 43.65
|
PRIMARY outcome
Timeframe: Blood collected on Day 1Groups will be compared on a quantitative allostatic load (AL) index integrating baseline fasting measures of neuroendocrine, immune and metabolic systems, urinary catecholamines, hematological measures, and hair/diurnal cortisol levels. 32 different biomarkers were analyzed for this outcome. The full range of the allostatic load index score is 0 to 32. A lower score is considered better, and a higher score is considered worse.
Outcome measures
| Measure |
Healthy Controls
n=70 Participants
No diagnosis of mitochondrial disease
|
Mutation
n=20 Participants
Participants carrying the m.3243A\>G point mutation, without a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
Deletion
n=15 Participants
Participants carrying a single, large-scale mtDNA deletion
|
Mutation With MELAS
n=5 Participants
Participants carrying the m.3243A\>G point mutation, with a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
|---|---|---|---|---|
|
Average Allostatic Load Index
|
9.10 allostatic load score
Standard Deviation 3.81
|
10.74 allostatic load score
Standard Deviation 4.05
|
11.31 allostatic load score
Standard Deviation 3.61
|
12.00 allostatic load score
Standard Deviation 4.08
|
SECONDARY outcome
Timeframe: Baseline and 2 hours post challenge on Day 1Groups will be compared on heart rate (HR) as a measure of cardiovascular reactivity to stress, monitored using a continuous 3-lead ECG. The elevation will be computed from the baseline HR to the peak HR reached during the TSST.
Outcome measures
| Measure |
Healthy Controls
n=70 Participants
No diagnosis of mitochondrial disease
|
Mutation
n=20 Participants
Participants carrying the m.3243A\>G point mutation, without a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
Deletion
n=15 Participants
Participants carrying a single, large-scale mtDNA deletion
|
Mutation With MELAS
n=5 Participants
Participants carrying the m.3243A\>G point mutation, with a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
|---|---|---|---|---|
|
Average TSST-induced Elevation in Heart Rate
|
14.8 beats per minute
Standard Deviation 12.4
|
12.4 beats per minute
Standard Deviation 10.7
|
10.9 beats per minute
Standard Deviation 6.41
|
12.7 beats per minute
Standard Deviation 10.1
|
SECONDARY outcome
Timeframe: Day 1The association between mitochondrial respiration using extracellular flux analysis (Seahorse) on blood lymphocytes, and anxiety symptoms measured using the state and trait anxiety inventory (STAI), will be quantified by a linear regression across all study participants.
Outcome measures
| Measure |
Healthy Controls
n=70 Participants
No diagnosis of mitochondrial disease
|
Mutation
n=20 Participants
Participants carrying the m.3243A\>G point mutation, without a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
Deletion
n=15 Participants
Participants carrying a single, large-scale mtDNA deletion
|
Mutation With MELAS
n=5 Participants
Participants carrying the m.3243A\>G point mutation, with a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
|---|---|---|---|---|
|
Correlation Between Anxiety and Mitochondrial Respiration
Correlation between mitochondrial respiration and state anxiety
|
0.10 coefficient of determination (R^2)
|
0.04 coefficient of determination (R^2)
|
0.01 coefficient of determination (R^2)
|
0.22 coefficient of determination (R^2)
|
|
Correlation Between Anxiety and Mitochondrial Respiration
Correlation between mitochondrial respiration and trait anxiety
|
0.04 coefficient of determination (R^2)
|
0.003 coefficient of determination (R^2)
|
0.334 coefficient of determination (R^2)
|
0.02 coefficient of determination (R^2)
|
SECONDARY outcome
Timeframe: Day 2 neuropsychological sessionThe fluency/initiation domain of executive functioning was assessed using the Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Test, specifically Condition 1: Letter Fluency total correct. Raw scores were converted to Z-scores based on the control group. A Z-score of 0 represents the mean of the control group, with positive values indicating better performance and negative values indicating worse performance.
Outcome measures
| Measure |
Healthy Controls
n=70 Participants
No diagnosis of mitochondrial disease
|
Mutation
n=20 Participants
Participants carrying the m.3243A\>G point mutation, without a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
Deletion
n=15 Participants
Participants carrying a single, large-scale mtDNA deletion
|
Mutation With MELAS
n=5 Participants
Participants carrying the m.3243A\>G point mutation, with a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes)
|
|---|---|---|---|---|
|
Average Neuropsychological Function
|
0.00 Z-score
Standard Deviation 1.0
|
-0.14 Z-score
Standard Deviation 0.96
|
-0.58 Z-score
Standard Deviation 1.35
|
-0.26 Z-score
Standard Deviation 1.52
|
Adverse Events
Healthy Controls
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Mutation
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Deletion
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Mutation With MELAS
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place