Mitochondrial Stress, Brain Imaging, and Epigenetics

NCT04831424 | Completed Results

• 2 other identifiers: NYSPI 74245R01MH122706
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Mitochondrial Diseases

Keywords

Mitochondria; Brain Imaging; Psychophysiology; Epigenetics; Stress; Metabolic rate; Mitochondrial function

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Blood collected on Day 1

Secondary Outcomes (3)

• Average TSST-induced Elevation in Heart Rate

  Baseline and 2 hours post challenge on Day 1

• Correlation Between Anxiety and Mitochondrial Respiration

  Day 1

• Average Neuropsychological Function

  Day 2 neuropsychological session

Study Arms (4)

Healthy controls

EXPERIMENTAL

No diagnosis of mitochondrial disease

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)

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)

Behavioral: Trier social stress test

Deletion

EXPERIMENTAL

Participants carrying a single, large-scale mtDNA deletion

Behavioral: Trier social stress test

Interventions

Trier social stress test BEHAVIORAL

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.

Also known as: TSST

Deletion; Healthy controls; Mutation; Mutation with MELAS

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Columbia University: lead
• Dartmouth College: collaborator
• Centre National de la Recherche Scientifique, France: collaborator
• Massachusetts General Hospital: collaborator
• Technische Universität Dresden: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Related Links

• Study Brochure

MeSH Terms

Conditions

Mitochondrial Diseases

Interventions

Psychological Tests

Condition Hierarchy (Ancestors)

Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities

Results Point of Contact

• Title: Martin Picard
• Organization: Columbia University

mp3484@columbia.edu

6467748967

Study Officials

• Martin Picard, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Behavioral Medicine (in Psychiatry and Neurology)

Model Details: 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).

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 5, 2021
• Study Start: June 12, 2018
• Primary Completion: June 30, 2023
• Study Completion: May 3, 2024
• Last Updated: May 20, 2025
• Results First Posted: April 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Data will be made available at the end of the study, without a expiry date.
• Access Criteria: Access will be handled through the NIMH Data Archive (NDA)

Locations

US (1)