Mitochondrial DiseasesMITO-OB-RESNCT06080568
Human Mitochondrial Stress-driven Obesity Resistance
An observational study of Mitochondrial Diseases and Mitochondrial Myopathies, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
Trial summary
The overarching aim of this observational study is to determine alterations in energy balance while exploring the underlying cellular mechanisms in human genetic models of mitochondrial stress. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Diseases, Mitochondrial Myopathies, Mitochondrial Disorder
- How many people
- 30 participants
- Where
- 1 siteDenmark
- Study dates
- 20 Oct 2023to 20 Dec 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Individuals with mitochondrial myopathy due to pathogenic mtDNA mutations are identified and recruited from the Copenhagen Neuromuscular Center or the Department of Clinical Genetics (Rigshospitalet). Control volunteers are recruited via recruitment announcements in Denmark.
Who may be able to join
- Known mtDNA point mutations
Who cannot join
- Use of antiarrhythmic medications or other medications which, in the opinion of the investigators, have the potential to affect outcome measures.
- Diagnosed severe heart disease, dysregulated thyroid gland conditions, or other dysregulated endocrinopathies, or other conditions which, in the opinion of the investigators, have the potential to affect outcome measures.
- Pregnancy
- Eligibility criteria for controls
- Current and regular use of antidiabetic medications or other medications which, in the opinion of the investigators, have the potential to affect outcome measures.
- Diagnosed heart disease, symptomatic asthma, liver cirrhosis or -failure, chronic kidney disease, dysregulated thyroid gland conditions or other dysregulated endocrinopathies, or other conditions which, in the opinion of the investigators, have the potential to affect outcome measures
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- Daily use of tobacco products
- Excessive alcohol consumption
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Energy Balance and Mitochondrial Function in Human Genetic Models of Mitochondrial Stress-mediated Obesity Resistance
The overarching aim of this observational study is to determine alterations in energy balance while exploring the underlying cellular mechanisms in human genetic models of mitochondrial stress.
In a case-control design, individuals with pathogenic mitochondrial DNA mutations will be compared to healthy controls matched for sex, age, and physical activity level. Participants will attend a screening visit and an experimental trial including assessments of energy expenditure, appetite sensation, energy intake, and muscle and subcutaneous adipose tissue biopsy samples.
Read the detailed description
Background: Pre-clinical models of mitochondrial stress are resistant to diet-induced obesity. Likewise, humans with primary mitochondrial diseases present a high prevalence of underweight (42%) as compared to a very low prevalence of obesity (2%). In this direction, recent data show a lower BMI across 17 cohorts of patients with mitochondrial diseases compared to national averages, suggesting mitochondrial stress-induced increments in resting energy expenditure as the primary driver of the lean phenotype. In recent years, the study of humans with genetic mutations has shown enormous potential to establish the mechanistic link between two physiological variables; indeed, if the mutation has a functional impact on one of those variables, then the direction of causality can be readily ascribed. Taken together, studies integrating assessments of energy balance with mitochondrial phenotyping in patients with rare mitochondrial disorders hold the potential to uncover putative mechanisms conferring protection from obesity in humans.
Objective: To determine alterations in energy expenditure/intake while exploring the underlying cellular mechanisms in individuals harboring mitochondrial DNA (mtDNA) mutations associated with mitochondrial stress.
Study design: Case-control study in individuals with mtDNA mutations (n=15) and healthy controls (n=15) matched for sex, age, and physical activity level.
Endpoint: Differences between individuals with mtDNA mutations and controls.
- Keywords
- Energy balance, Energy expenditure, Appetite, Energy intake, Mitochondrial dysfunction
- Medical subject headings
- Mitochondrial Diseases, Mitochondrial Myopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Mitochondrial myopathy | Individuals with pathogenic mtDNA mutations | |
| Control | Individuals without mtDNA mutations |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resting energy expenditure
Resting energy expenditure is measured in the fasting and fed state by indirect calorimetry
Measured: Before (baseline) and 60-180 minutes after ingestion of a glucose solution
Appetite
Subjective appetite sensations are measured in the fasting and fed state by visual analogue scale (VAS) ratings
Measured: Before (baseline) and 60-180 minutes after ingestion of a glucose solution as well as immediately after an ad libitum meal test
Energy intake
Energy intake is measured by quantifying the amount of food ingested during an ad libitum meal test
Measured: 180 minutes after ingestion of a glucose solution
Secondary outcomes (5)
Plasma hormones and cytokines modulating appetite and energy expenditure
Plasma levels of FGF21, GDF15, GLP-1, PYY, ghrelin, glucagon, and GIP are measured in the fasting and fed state
Measured: Before (baseline) and 0-180 minutes after ingestion of a glucose solution
Plasma adipokines modulating appetite and energy expenditure
Plasma levels of leptin and adiponectin are measured in the fasting state
Measured: Baseline
Muscle mitochondrial leak respiration
Mitochondrial O2 flux is measured by high-resolution respirometry in permeabilized muscle fibers
Measured: Baseline
Muscle mitochondrial efficiency
Mitochondrial P/O ratio is measured by high-resolution respirometry in isolated mitochondria
Measured: Baseline
Muscle mitochondrial membrane potential
Mitochondrial membrane potential is measured by high-resolution fluorometry in isolated mitochondria
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2023
- Study start20 Oct 2023
- Primary completion20 Dec 2024
- Study completion20 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- University of Copenhagen
- Responsible party
- Principal investigator, Matteo Fiorenza, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Matteo Fiorenza, Ph.D., Principal investigator, Copenhagen University Hospital, RigshospitaletJohn Vissing, MD, Principal investigator, Copenhagen University Hospital, RigshospitaletSigne Torekov, Ph.D., Principal investigator, University of Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06080568
- Sponsor's protocol ID
- MITO-OB-RES
- Acronym
- MITO-OB-RES
- Status last verified
- Jun 2025
- First submitted
- 29 Sep 2023
- Last updated
- 22 Jun 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Guo Q, Xu Z, Zhou D, Fu T, Wang W, Sun W, Xiao L, Liu L, Ding C, Yin Y, Zhou Z, Sun Z, Zhu Y, Zhou W, Jia Y, Xue J, Chen Y, Chen XW, Piao HL, Lu B, Gan Z. Mitochondrial proteostasis stress in muscle drives a long-range protective response to alleviate dietary obesity independently of ATF4. Sci Adv. 2022 Jul 29;8(30):eabo0340. doi: 10.1126/sciadv.abo0340. Epub 2022 Jul 27.
PubMed 35895846Yang M, Xu L, Xu C, Cui Y, Jiang S, Dong J, Liao L. The Mutations and Clinical Variability in Maternally Inherited Diabetes and Deafness: An Analysis of 161 Patients. Front Endocrinol (Lausanne). 2021 Nov 25;12:728043. doi: 10.3389/fendo.2021.728043. eCollection 2021.
PubMed 34899594Sturm G, Karan KR, Monzel AS, Santhanam B, Taivassalo T, Bris C, Ware SA, Cross M, Towheed A, Higgins-Chen A, McManus MJ, Cardenas A, Lin J, Epel ES, Rahman S, Vissing J, Grassi B, Levine M, Horvath S, Haller RG, Lenaers G, Wallace DC, St-Onge MP, Tavazoie S, Procaccio V, Kaufman BA, Seifert EL, Hirano M, Picard M. OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases. Commun Biol. 2023 Jan 12;6(1):22. doi: 10.1038/s42003-022-04303-x.
PubMed 36635485O'Rahilly S. "Treasure Your Exceptions"-Studying Human Extreme Phenotypes to Illuminate Metabolic Health and Disease: The 2019 Banting Medal for Scientific Achievement Lecture. Diabetes. 2021 Jan;70(1):29-38. doi: 10.2337/dbi19-0037.
PubMed 33355307Saleheen D, Natarajan P, Armean IM, Zhao W, Rasheed A, Khetarpal SA, Won HH, Karczewski KJ, O'Donnell-Luria AH, Samocha KE, Weisburd B, Gupta N, Zaidi M, Samuel M, Imran A, Abbas S, Majeed F, Ishaq M, Akhtar S, Trindade K, Mucksavage M, Qamar N, Zaman KS, Yaqoob Z, Saghir T, Rizvi SNH, Memon A, Hayyat Mallick N, Ishaq M, Rasheed SZ, Memon FU, Mahmood K, Ahmed N, Do R, Krauss RM, MacArthur DG, Gabriel S, Lander ES, Daly MJ, Frossard P, Danesh J, Rader DJ, Kathiresan S. Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity. Nature. 2017 Apr 12;544(7649):235-239. doi: 10.1038/nature22034.
PubMed 28406212
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Energy Balance and Mitochondrial Function in Human Genetic Models of Mitochondrial Stress-mediated Obesity Resistance
- ClinicalTrials.gov ID
- NCT06080568
- Acronym / sponsor ID
- MITO-OB-RES / MITO-OB-RES
- Keywords
- Energy balance, Energy expenditure, Appetite, Energy intake, Mitochondrial dysfunction
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- University of Copenhagen
- Study start
- 20 Oct 2023 (actual)
- Primary completion
- 20 Dec 2024 (actual)
- Study completion
- 20 Dec 2024 (actual)
- First posted
- 12 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The overarching aim of this observational study is to determine alterations in energy balance while exploring the underlying cellular mechanisms in human genetic models of mitochondrial stress.
In a case-control design, individuals with pathogenic mitochondrial DNA mutations will be compared to healthy controls matched for sex, age, and physical activity level. Participants will attend a screening visit and an experimental trial including assessments of energy expenditure, appetite sensation, energy intake, and muscle and subcutaneous adipose tissue biopsy samples.
Detailed description
Background: Pre-clinical models of mitochondrial stress are resistant to diet-induced obesity. Likewise, humans with primary mitochondrial diseases present a high prevalence of underweight (42%) as compared to a very low prevalence of obesity (2%). In this direction, recent data show a lower BMI across 17 cohorts of patients with mitochondrial diseases compared to national averages, suggesting mitochondrial stress-induced increments in resting energy expenditure as the primary driver of the lean phenotype. In recent years, the study of humans with genetic mutations has shown enormous potential to establish the mechanistic link between two physiological variables; indeed, if the mutation has a functional impact on one of those variables, then the direction of causality can be readily ascribed. Taken together, studies integrating assessments of energy balance with mitochondrial phenotyping in patients with rare mitochondrial disorders hold the potential to uncover putative mechanisms conferring protection from obesity in humans.
Objective: To determine alterations in energy expenditure/intake while exploring the underlying cellular mechanisms in individuals harboring mitochondrial DNA (mtDNA) mutations associated with mitochondrial stress.
Study design: Case-control study in individuals with mtDNA mutations (n=15) and healthy controls (n=15) matched for sex, age, and physical activity level.
Endpoint: Differences between individuals with mtDNA mutations and controls.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mitochondrial myopathy | – | –Individuals with pathogenic mtDNA mutations |
| Control | – | –Individuals without mtDNA mutations |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Individuals with mitochondrial myopathy due to pathogenic mtDNA mutations are identified and recruited from the Copenhagen Neuromuscular Center or the Department of Clinical Genetics (Rigshospitalet). Control volunteers are recruited via recruitment announcements in Denmark.
Key inclusion criteria (1 listed)
- Known mtDNA point mutations
Key exclusion criteria (9 listed)
- Use of antiarrhythmic medications or other medications which, in the opinion of the investigators, have the potential to affect outcome measures.
- Diagnosed severe heart disease, dysregulated thyroid gland conditions, or other dysregulated endocrinopathies, or other conditions which, in the opinion of the investigators, have the potential to affect outcome measures.
- Pregnancy
- Eligibility criteria for controls
- Current and regular use of antidiabetic medications or other medications which, in the opinion of the investigators, have the potential to affect outcome measures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Resting energy expenditure
Time frame: Before (baseline) and 60-180 minutes after ingestion of a glucose solution
Resting energy expenditure is measured in the fasting and fed state by indirect calorimetry
Appetite
Time frame: Before (baseline) and 60-180 minutes after ingestion of a glucose solution as well as immediately after an ad libitum meal test
Subjective appetite sensations are measured in the fasting and fed state by visual analogue scale (VAS) ratings
Energy intake
Time frame: 180 minutes after ingestion of a glucose solution
Energy intake is measured by quantifying the amount of food ingested during an ad libitum meal test
5 secondary outcomes
Plasma hormones and cytokines modulating appetite and energy expenditure
Time frame: Before (baseline) and 0-180 minutes after ingestion of a glucose solution
Plasma adipokines modulating appetite and energy expenditure
Time frame: Baseline
Muscle mitochondrial leak respiration
Time frame: Baseline
Muscle mitochondrial efficiency
Time frame: Baseline
Muscle mitochondrial membrane potential
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2025.
- Background: PubMed 35895846Guo Q, Xu Z, Zhou D, Fu T, Wang W, Sun W, Xiao L, Liu L, Ding C, Yin Y, Zhou Z, Sun Z, Zhu Y, Zhou W, Jia Y, Xue J, Chen Y, Chen XW, Piao HL, Lu B, Gan Z. Mitochondrial proteostasis stress in muscle drives a long-range protective response to alleviate dietary obesity independently of ATF4. Sci Adv. 2022 Jul 29;8(30):eabo0340. doi: 10.1126/sciadv.abo0340. Epub 2022 Jul 27.
- Background: PubMed 34899594Yang M, Xu L, Xu C, Cui Y, Jiang S, Dong J, Liao L. The Mutations and Clinical Variability in Maternally Inherited Diabetes and Deafness: An Analysis of 161 Patients. Front Endocrinol (Lausanne). 2021 Nov 25;12:728043. doi: 10.3389/fendo.2021.728043. eCollection 2021.
- Background: PubMed 36635485Sturm G, Karan KR, Monzel AS, Santhanam B, Taivassalo T, Bris C, Ware SA, Cross M, Towheed A, Higgins-Chen A, McManus MJ, Cardenas A, Lin J, Epel ES, Rahman S, Vissing J, Grassi B, Levine M, Horvath S, Haller RG, Lenaers G, Wallace DC, St-Onge MP, Tavazoie S, Procaccio V, Kaufman BA, Seifert EL, Hirano M, Picard M. OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases. Commun Biol. 2023 Jan 12;6(1):22. doi: 10.1038/s42003-022-04303-x.
- Background: PubMed 33355307O'Rahilly S. "Treasure Your Exceptions"-Studying Human Extreme Phenotypes to Illuminate Metabolic Health and Disease: The 2019 Banting Medal for Scientific Achievement Lecture. Diabetes. 2021 Jan;70(1):29-38. doi: 10.2337/dbi19-0037.
- Background: PubMed 28406212Saleheen D, Natarajan P, Armean IM, Zhao W, Rasheed A, Khetarpal SA, Won HH, Karczewski KJ, O'Donnell-Luria AH, Samocha KE, Weisburd B, Gupta N, Zaidi M, Samuel M, Imran A, Abbas S, Majeed F, Ishaq M, Akhtar S, Trindade K, Mucksavage M, Qamar N, Zaman KS, Yaqoob Z, Saghir T, Rizvi SNH, Memon A, Hayyat Mallick N, Ishaq M, Rasheed SZ, Memon FU, Mahmood K, Ahmed N, Do R, Krauss RM, MacArthur DG, Gabriel S, Lander ES, Daly MJ, Frossard P, Danesh J, Rader DJ, Kathiresan S. Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity. Nature. 2017 Apr 12;544(7649):235-239. doi: 10.1038/nature22034.
- Individual participant dataSharing planned: No
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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.
Matteo Fiorenza, Ph.D. principal investigator
Copenhagen University Hospital, Rigshospitalet
John Vissing, MD principal investigator
Copenhagen University Hospital, Rigshospitalet
Signe Torekov, Ph.D. principal investigator
University of Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Mitochondrial Diseases and Mitochondrial Myopathies, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.
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 1 inclusion and 9 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 22 Jun 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 Denmark. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Resting energy expenditure (time frame: Before (baseline) and 60-180 minutes after ingestion of a glucose solution). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06080568, which also lists 5 linked publications.
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 22 Jun 2025; AzTrials last refreshed its copy on 3 Nov 2026.