Mitochondrial DiseasesMiSBIENCT04831424
Mitochondrial Stress, Brain Imaging, and Epigenetics
A study testing Trier social stress test in people with Mitochondrial Diseases, run by Columbia University at 1 site in United States.
Trial summary
The MiSBIE study collects biological, behavioral, psychosocial, neuropsychological, and brain imaging data in participants with either: normal mitochondrial function, individuals with the m.3243A>G mitochondrial DNA (mtDNA) mutation, and individuals a single large-scale mtDNA deletion. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Diseases
- What is being tested?
- Trier social stress test
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jun 2018to 3 May 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women patients between 18 and 55 years of age
- Willing to provide saliva samples and have venous catheter installed for blood collection during the hospital visit
- Willing to provide informed consent and capacity to consent
- Use of effective method of birth control for women of childbearing capacity
- English Speaking
Who cannot join
- Individuals with cognitive deficit incapable of providing informed consent will not be included
- Symptoms of flu or other seasonal infection four weeks preceding hospital visit
- Raynaud's syndrome (Raynaud phenomenon)
- Involvement in any therapeutic trials listed on clinicaltrials.gov, including exercise
- Metal inside or outside the body or claustrophobia prohibitive to MRI testing
- Diagnosed with mitochondrial disease m.3243A>G, or large scale mtDNA deletion (for healthy controls)
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: The Mitochondrial Stress, Brain Imaging, and Epigenetics Study
The MiSBIE study collects biological, behavioral, psychosocial, neuropsychological, and brain imaging data in participants with either: normal mitochondrial function, individuals with the m.3243A>G mitochondrial DNA (mtDNA) mutation, and individuals a single large-scale mtDNA deletion. These defects induce mitochondrial allostatic load (MAL). The 2-day protocol, plus home-based data collection, will provide a comprehensive assessment of the multi-systemic dysregulation associated with MAL or mitochondrial dysfunction, and the link to physical and mental health-related symptoms.
Aim 1: Determine the influence of MAL on systemic AL biomarkers.
Read more
Aim 2: Establish the influence of MAL on stress reactivity profiles.
Aim 3. Examine the association between MAL and psychological functioning.
Read the detailed description
Age-related physical and cognitive decline, as well as the risk of neurological diseases, are increased by the effects of psychosocial stress. Psychosocial stress triggers neuroendocrine, metabolic, cardiovascular, and inflammatory changes in the body. These changes vary in nature and magnitude between individuals, and are associated with long-term disease risk. However, the biological determinants of the stress response are not well understood.
This project aims to translate the preclinical findings (how mitochondria regulate the different organ systems and major stress response axes are activated during psychological stress) by studying a population of individuals with varying degree of mitochondrial dysfunction, and to test potential neural mechanism, and why some individuals respond more strongly than others to the same stressor.
Each participant will be studied over two consecutive days. Participants will be housed on campus to standardize study conditions. On Day 1, participants will donate blood and saliva, undergo a neuropsychological assessment, and complete questionnaires to assess psychosocial functioning and psychiatric symptoms. After lunch, the investigator will monitor dynamic changes in mental health-related biological outcomes (positive and negative affect, circulating levels of the inflammatory cytokine IL-6, and salivary cortisol) in response to a standardized laboratory challenge. On Day 2, participants will undergo a medical evaluation to assess clinical symptoms and undergo a whole brain neuroimaging session where both resting and stress elicited activity will be measured. A variant of the same stressor as on Day 1 will be used in the neuroimaging session. Participants will then be debriefed, concluding the individuals participation in the study. Participants also complete a home-based saliva and stool collection to examine diurnal variation in salivary hormones, and to examine microbiome composition. This translational project will generate a unique combination of complimentary molecular, cellular, and neuroimaging data that will advance our understanding of the links between mitochondria, the brain, and mental health-related outcomes.
- Conditions
- Mitochondrial Diseases
- Being tested
- Trier social stress test
- Keywords
- Mitochondria, Brain Imaging, Psychophysiology, Epigenetics, Stress, Metabolic rate, Mitochondrial function
- Medical subject headings
- Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trier social stress testBehavioural
Also called TSST
The Trier social stress test (TSST) is a tool for investigating psychobiological stress responses in a laboratory setting. It is a laboratory procedure used to reliably induce stress in human research participants. The study is not examining or validating the test itself but rather using it as a tool to measure the response/focus of study.
| Study group | Role | What they receive |
|---|---|---|
| Healthy controls | Experimental | No diagnosis of mitochondrial disease Receives: Behavioral: Trier social stress test |
| Mutation | Experimental | Participants carrying the m.3243A>G point mutation, without a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) Receives: Behavioral: Trier social stress test |
| Mutation with MELAS | Experimental | Participants carrying the m.3243A>G point mutation, with a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) Receives: Behavioral: Trier social stress test |
| Deletion | Experimental | Participants carrying a single, large-scale mtDNA deletion Receives: Behavioral: Trier social stress test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average TSST-induced Elevation in Cortisol
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.
Measured: Day 1 post challenge (approximately 2 hours)
Average Allostatic Load Index
Groups 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.
Measured: Blood collected on Day 1
Secondary outcomes (3)
Average TSST-induced Elevation in Heart Rate
Groups 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.
Measured: Baseline and 2 hours post challenge on Day 1
Correlation Between Anxiety and Mitochondrial Respiration
The 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.
Measured: Day 1
Average Neuropsychological Function
The 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.
Measured: Day 2 neuropsychological session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2021
- Study start12 Jun 2018
- Primary completion30 Jun 2023
- Study completion3 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All participants will undergo TSST and have samples With DNA collected (blood plasma and serum, purified leukocytes, saliva, urine, buccal epithelial cells, hair are stored).
- Masking
- None (open label)
- Enrolment
- 110 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Dartmouth College, Centre National de la Recherche Scientifique, France, Massachusetts General Hospital, Technische Universität Dresden, National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Martin Picard, Columbia University
- Investigators
- Martin Picard, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04831424
- Sponsor's protocol ID
- NYSPI 7424
- Other IDs
- 5R01MH122706
- Acronym
- MiSBIE
- Status last verified
- May 2025
- First submitted
- 31 Mar 2021
- Last updated
- 20 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All data will be deposited to the NIMH Data Archive.
Study at a glance
From the registry record, last updated by the sponsor on 20 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Mitochondrial Stress, Brain Imaging, and Epigenetics Study
- ClinicalTrials.gov ID
- NCT04831424
- Acronym / sponsor ID
- MiSBIE / NYSPI 7424
- Conditions
- Mitochondrial Diseases
- Keywords
- Mitochondria, Brain Imaging, Psychophysiology, Epigenetics, Stress, Metabolic rate, Mitochondrial function
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Dartmouth College, Centre National de la Recherche Scientifique, France, Massachusetts General Hospital, Technische Universität Dresden, National Institute of Mental Health (NIMH)
- Study start
- 12 Jun 2018 (actual)
- Primary completion
- 30 Jun 2023 (actual)
- Study completion
- 3 May 2024 (actual)
- First posted
- 5 Apr 2021 (actual)
- Results
- Posted 15 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The MiSBIE study collects biological, behavioral, psychosocial, neuropsychological, and brain imaging data in participants with either: normal mitochondrial function, individuals with the m.3243A>G mitochondrial DNA (mtDNA) mutation, and individuals a single large-scale mtDNA deletion. These defects induce mitochondrial allostatic load (MAL). The 2-day protocol, plus home-based data collection, will provide a comprehensive assessment of the multi-systemic dysregulation associated with MAL or mitochondrial dysfunction, and the link to physical and mental health-related symptoms.
Aim 1: Determine the influence of MAL on systemic AL biomarkers.
Aim 2: Establish the influence of MAL on stress reactivity profiles.
Aim 3. Examine the association between MAL and psychological functioning.
Detailed description
Age-related physical and cognitive decline, as well as the risk of neurological diseases, are increased by the effects of psychosocial stress. Psychosocial stress triggers neuroendocrine, metabolic, cardiovascular, and inflammatory changes in the body. These changes vary in nature and magnitude between individuals, and are associated with long-term disease risk. However, the biological determinants of the stress response are not well understood.
This project aims to translate the preclinical findings (how mitochondria regulate the different organ systems and major stress response axes are activated during psychological stress) by studying a population of individuals with varying degree of mitochondrial dysfunction, and to test potential neural mechanism, and why some individuals respond more strongly than others to the same stressor.
Each participant will be studied over two consecutive days. Participants will be housed on campus to standardize study conditions. On Day 1, participants will donate blood and saliva, undergo a neuropsychological assessment, and complete questionnaires to assess psychosocial functioning and psychiatric symptoms. After lunch, the investigator will monitor dynamic changes in mental health-related biological outcomes (positive and negative affect, circulating levels of the inflammatory cytokine IL-6, and salivary cortisol) in response to a standardized laboratory challenge. On Day 2, participants will undergo a medical evaluation to assess clinical symptoms and undergo a whole brain neuroimaging session where both resting and stress elicited activity will be measured. A variant of the same stressor as on Day 1 will be used in the neuroimaging session. Participants will then be debriefed, concluding the individuals participation in the study. Participants also complete a home-based saliva and stool collection to examine diurnal variation in salivary hormones, and to examine microbiome composition. This translational project will generate a unique combination of complimentary molecular, cellular, and neuroimaging data that will advance our understanding of the links between mitochondria, the brain, and mental health-related outcomes.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- All participants will undergo TSST and have samples With DNA collected (blood plasma and serum, purified leukocytes, saliva, urine, buccal epithelial cells, hair are stored).
| Arm | Type | Receives |
|---|---|---|
| Healthy controls | Experimental | Behavioral: Trier social stress testNo diagnosis of mitochondrial disease |
| Mutation | Experimental | Behavioral: Trier social stress testParticipants carrying the m.3243A>G point mutation, without a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) |
| Mutation with MELAS | Experimental | Behavioral: Trier social stress testParticipants carrying the m.3243A>G point mutation, with a diagnosis of MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) |
| Deletion | Experimental | Behavioral: Trier social stress testParticipants carrying a single, large-scale mtDNA deletion |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Men and women patients between 18 and 55 years of age
- Willing to provide saliva samples and have venous catheter installed for blood collection during the hospital visit
- Willing to provide informed consent and capacity to consent
- Use of effective method of birth control for women of childbearing capacity
- English Speaking
Key exclusion criteria (6 listed)
- Individuals with cognitive deficit incapable of providing informed consent will not be included
- Symptoms of flu or other seasonal infection four weeks preceding hospital visit
- Raynaud's syndrome (Raynaud phenomenon)
- Involvement in any therapeutic trials listed on clinicaltrials.gov, including exercise
- Metal inside or outside the body or claustrophobia prohibitive to MRI testing
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 |
|---|---|---|
| Trier social stress testAlso: TSSTThe Trier social stress test (TSST) is a tool for investigating psychobiological stress responses in a laboratory setting. It is a laboratory procedure used to reliably induce stress in human research participants. The study is not examining or validating the test itself but rather using it as a tool to measure the response/focus of study. | Behavioural | Deletion, Healthy controls, Mutation, Mutation with MELAS |
Primary outcome
Average TSST-induced Elevation in Cortisol
Time frame: 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.
Average Allostatic Load Index
Time frame: Blood collected on Day 1
Groups 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.
3 secondary outcomes
Average TSST-induced Elevation in Heart Rate
Time frame: Baseline and 2 hours post challenge on Day 1
Correlation Between Anxiety and Mitochondrial Respiration
Time frame: Day 1
Average Neuropsychological Function
Time frame: Day 2 neuropsychological session
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Study BrochureLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All data will be deposited to the NIMH Data Archive.
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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.
Martin Picard, PhD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Trier social stress test in people with Mitochondrial Diseases, run by Columbia University at 1 site in United States.
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 5 inclusion and 6 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 20 May 2025. 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 United States. 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?
Yes. Results are posted in the registry (first posted 15 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Average TSST-induced Elevation in Cortisol (time frame: Day 1 post challenge (approximately 2 hours)). The study lists 2 primary outcomes in all. 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 20 May 2025.