Mitochondrial DNA DeletionPhase 1NCT06186154
Vitamin B12 and Folinic Acid Supplementation in Mitochondrial DNA Deletion Syndromes
A Phase 1 study testing Folinic acid (oral); Cyanocobalamin sublingual in people with Mitochondrial DNA Deletion and Macrocytosis, run by University of British Columbia.
Trial summary
The purpose of this single center study is to evaluate whether there is a concordant improvement in macrocytosis in patient with mtDNA deletions with established macrocytosis following a trial of Vitamin B12 and Folinic acid supplementation. Read more about this study
- Who is it for?
- Ages 19 years and older
- Conditions the study is for
- Mitochondrial DNA Deletion, Macrocytosis
- What is being tested?
- Folinic acid (oral); Cyanocobalamin sublingual
- Type of treatment
- Pill or oral medicine
- How many people
- 25 participants
- Where
- No sites listed yet
- Study dates
- Jan 2024to Mar 2025
- Phase
- Phase 1
- 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 19 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages eligible for study: 19 years and older (Adult, Older Adult)
- All subjects reviewed previously at the Adult Metabolic Diseases Clinic with clinical features characteristic of major mtDNA deletion cases with biochemical macrocytosis
- Continue prior administration of other therapies pertaining to their necessary medical care
- Subjects must be clinically stable for more than one month after any stroke-like episodes
- Written, informed consent to participate in the study
Who cannot join
- Subjects with mitochondrial disease with a genetic etiology other than a major mtDNA deletion
- Palliative care patients
- Patients with a progressive neurologic disorder clinically attributable to a cause other than mitochondrial disease (e.g., ischemic stroke due to embolism from atrial fibrillation, atherosclerosis, malignant hypertension,)
- Subjects who decline blood test and/or the follow-up schedule
- Inability or refusal to give informed consent
- Coexisting participation with other investigational drug study
About this study
The purpose of this single center study is to evaluate whether there is a concordant improvement in macrocytosis in patient with mtDNA deletions with established macrocytosis following a trial of Vitamin B12 and Folinic acid supplementation.
This study aims to assess if macrocytosis in patients with mtDNA deletion syndromes improve following empiric supplementation with vitamin B12 and folic acid. Complete blood counts (CBC) will be followed during this study (at initiation, 3 months, and 6 months) to assess for response in MCV to supplementation. The potential involvement of the region affected by the mtDNA deletion in mitochondrial folate-mediated transport and metabolism [5,6] may serve as the possible link between the deletion and observed macrocytosis.
Read more
Neurologic/cognitive outcomes will also be followed at the above time intervals to assess if 3-6 months of Vitamin B12/folinic supplementation is an adequate vs insufficient time to observe a change in the Newcastle Mitochondrion Disease Adult Scale (NMDAS). The value of this study is that it may produce pilot data to support empiric supplementation of B12 and folate for patients with macrocytosis and mtDNA deletion syndromes.
Disease Large single mtDNA (mitochondrial DNA) deletion syndrome is a rare inborn error of metabolism, and chronic progressive external ophthalmoplegia (CPEO) is the most common phenotype in adults with this form of mitochondrial deletino syndrome. Upon recent review of cases from our Adult Metabolic Diseases Clinic (AMDC), several patients with mtDNA deletion syndromes (as opposed to mtDNA missense mutations identified over the same 2016-2022-year period) were found to have unexplained macrocytosis and this is the relevant study population for this assessment.
Intervention Participants will be followed as a single group for this pilot study. The study will include two phases; 6 months without micronutrient supplementation, followed by 6 months of folinic acid and B12 supplementation. Subjects will have bloodwork to establish baseline complete blood count (macrocytosis with/without anemia) as well as at 3 and 6 months without supplementation to establish a trend in the hematologic parameters above. Participants will also complete a baseline Newcastle Mitochondrion Disease Adult Scale (NMDAS) prior to supplementation, as well as at 3 and 6 months of starting supplementation. This next phase of folinic acid and B12 supplementation will continue for 6 months with biomarker monitoring again at 9 and 12 months, and the same biochemical investigations will take place to assess if there was a true association between peripheral serum macrocytosis and nutrient supplementation during the time periods.
Phase
1
Read the detailed description
Study Design:
- Study type: Pilot single group study
- Actual Enrollment: 25 participants
- Allocation: N/A
- Intervention Model: Single Group Assignment
- Intervention Model Description:
- Vitamin B12 (also known as Cyanocobalamin) daily sublingual supplementation of 1000 mcg/day and folinic acid orally 1mg/day
- Laboratory: Complete blood count, electrolytes, reticulocytes, creatinine, urea, alkaline phosphatase (ALP), alanine transaminase, ferritin, total homocysteine, lactate and hemoglobin A1c. Routine blood will be collected as regular standard of care with each visit. MMA will also be assessed. Peripheral serum values (CBC, B12) will serve as a representation of central micronutrient availability
- Clinical Evaluation: the Newcastle mitochondrial disease adult scale (NMDAS)
- Masking: None (Open Label)
- Primary Purpose:
- Assess for the proportion of subjects whose macrocytosis corrects (MCV, measured in fL, returns to the normal range of the testing laboratory) with Vitamin B12 and folinic acid supplementation in patient population with mtDNA deletion syndrome
- Follow the Newcastle mitochondrial disease adult scale (NMDAS) with Vitamin B12 and folinic acid supplementation in patient population with mtDNA deletion syndromes for any clinical evidence of change.
The NMDAS has a maximum score of 140 (sections I, II (excluding question 8), and III). A higher score indicates more severe disease.
- Conditions
- Mitochondrial DNA Deletion, Macrocytosis
- Being tested
- Folinic acid (oral); Cyanocobalamin sublingual
- Keywords
- Folinic Acid, Vitamin B12, Mitochondrial DNA Deletion, Macrocytosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folinic acid (oral); Cyanocobalamin sublingualDietary supplement
- Vitamin B12 (also known as Cyanocobalamin) daily sublingual supplementation of 1000 mcg/day and folinic acid orally 1mg/day
- Laboratory: Complete blood count, electrolytes, reticulocytes, creatinine, urea, alkaline phosphatase (ALP), alanine transaminase, ferritin, total homocysteine, lactate and hemoglobin A1c. Routine blood will be collected as regular standard of care with each visit. MMA will also be assessed. Peripheral serum values (CBC, B12) will serve as a representation of central micronutrient availability
- Clinical Evaluation: the Newcastle mitochondrial disease adult scale (NMDAS)
What is being measured
The primary outcome is the main question the study is designed to answer.
Macrocytosis
- Proportion of patients who normalize their MCV (measured in fL) such that the MCV Is within the normal range of the testing laboratory after 6 months of vitamin therapy
Measured: 1 year
Secondary outcomes (1)
Newcastle mitochondrial disease adult scale (NMDAS)
NMDAS scores (sections I-III with the exception of question 8 in section II) at scheduled intervals to assess for any clinically-evident change following supplementation introduction. Total score 140. Higher score indicates more severe disease
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2023
- Study startJan 2024 (estimated)
- Primary completionJan 2025 (estimated)
- Study completionMar 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial DNA DeletionStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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 1
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Crossover
- Model description
- Pilot single group study where each study subject acts as their own control
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andre Mattman, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06186154
- Sponsor's protocol ID
- H23-02541
- Status last verified
- Dec 2023
- First submitted
- 1 Dec 2023
- Last updated
- 29 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin B12 and Folinic Acid Supplementation in Mitochondrial DNA Deletion Syndromes
- ClinicalTrials.gov ID
- NCT06186154
- Acronym / sponsor ID
- H23-02541
- Conditions
- Mitochondrial DNA Deletion, Macrocytosis
- Keywords
- Folinic Acid, Vitamin B12, Mitochondrial DNA Deletion, Macrocytosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- Jan 2024 (estimated)
- Primary completion
- Jan 2025 (estimated)
- Study completion
- Mar 2025 (estimated)
- First posted
- 29 Dec 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 purpose of this single center study is to evaluate whether there is a concordant improvement in macrocytosis in patient with mtDNA deletions with established macrocytosis following a trial of Vitamin B12 and Folinic acid supplementation.
This study aims to assess if macrocytosis in patients with mtDNA deletion syndromes improve following empiric supplementation with vitamin B12 and folic acid. Complete blood counts (CBC) will be followed during this study (at initiation, 3 months, and 6 months) to assess for response in MCV to supplementation. The potential involvement of the region affected by the mtDNA deletion in mitochondrial folate-mediated transport and metabolism [5,6] may serve as the possible link between the deletion and observed macrocytosis.
Neurologic/cognitive outcomes will also be followed at the above time intervals to assess if 3-6 months of Vitamin B12/folinic supplementation is an adequate vs insufficient time to observe a change in the Newcastle Mitochondrion Disease Adult Scale (NMDAS). The value of this study is that it may produce pilot data to support empiric supplementation of B12 and folate for patients with macrocytosis and mtDNA deletion syndromes.
Disease Large single mtDNA (mitochondrial DNA) deletion syndrome is a rare inborn error of metabolism, and chronic progressive external ophthalmoplegia (CPEO) is the most common phenotype in adults with this form of mitochondrial deletino syndrome. Upon recent review of cases from our Adult Metabolic Diseases Clinic (AMDC), several patients with mtDNA deletion syndromes (as opposed to mtDNA missense mutations identified over the same 2016-2022-year period) were found to have unexplained macrocytosis and this is the relevant study population for this assessment.
Intervention Participants will be followed as a single group for this pilot study. The study will include two phases; 6 months without micronutrient supplementation, followed by 6 months of folinic acid and B12 supplementation. Subjects will have bloodwork to establish baseline complete blood count (macrocytosis with/without anemia) as well as at 3 and 6 months without supplementation to establish a trend in the hematologic parameters above. Participants will also complete a baseline Newcastle Mitochondrion Disease Adult Scale (NMDAS) prior to supplementation, as well as at 3 and 6 months of starting supplementation. This next phase of folinic acid and B12 supplementation will continue for 6 months with biomarker monitoring again at 9 and 12 months, and the same biochemical investigations will take place to assess if there was a true association between peripheral serum macrocytosis and nutrient supplementation during the time periods.
Phase
1
Detailed description
Study Design:
- Study type: Pilot single group study
- Actual Enrollment: 25 participants
- Allocation: N/A
- Intervention Model: Single Group Assignment
- Intervention Model Description:
- Vitamin B12 (also known as Cyanocobalamin) daily sublingual supplementation of 1000 mcg/day and folinic acid orally 1mg/day
- Laboratory: Complete blood count, electrolytes, reticulocytes, creatinine, urea, alkaline phosphatase (ALP), alanine transaminase, ferritin, total homocysteine, lactate and hemoglobin A1c. Routine blood will be collected as regular standard of care with each visit. MMA will also be assessed. Peripheral serum values (CBC, B12) will serve as a representation of central micronutrient availability
- Clinical Evaluation: the Newcastle mitochondrial disease adult scale (NMDAS)
- Masking: None (Open Label)
- Primary Purpose:
- Assess for the proportion of subjects whose macrocytosis corrects (MCV, measured in fL, returns to the normal range of the testing laboratory) with Vitamin B12 and folinic acid supplementation in patient population with mtDNA deletion syndrome
- Follow the Newcastle mitochondrial disease adult scale (NMDAS) with Vitamin B12 and folinic acid supplementation in patient population with mtDNA deletion syndromes for any clinical evidence of change.
The NMDAS has a maximum score of 140 (sections I, II (excluding question 8), and III). A higher score indicates more severe disease.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Crossover
- Masking
- None (open label)
- Model description
- Pilot single group study where each study subject acts as their own control
Who may qualify
- Ages
- 19 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Ages eligible for study: 19 years and older (Adult, Older Adult)
- All subjects reviewed previously at the Adult Metabolic Diseases Clinic with clinical features characteristic of major mtDNA deletion cases with biochemical macrocytosis
- Continue prior administration of other therapies pertaining to their necessary medical care
- Subjects must be clinically stable for more than one month after any stroke-like episodes
- Written, informed consent to participate in the study
Key exclusion criteria (6 listed)
- Subjects with mitochondrial disease with a genetic etiology other than a major mtDNA deletion
- Palliative care patients
- Patients with a progressive neurologic disorder clinically attributable to a cause other than mitochondrial disease (e.g., ischemic stroke due to embolism from atrial fibrillation, atherosclerosis, malignant hypertension,)
- Subjects who decline blood test and/or the follow-up schedule
- Inability or refusal to give informed consent
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 |
|---|---|---|
| Folinic acid (oral); Cyanocobalamin sublingual* Vitamin B12 (also known as Cyanocobalamin) daily sublingual supplementation of 1000 mcg/day and folinic acid orally 1mg/day * Laboratory: Complete blood count, electrolytes, reticulocytes, creatinine, urea, alkaline phosphatase (ALP), alanine transaminase, ferritin, total homocysteine, lactate and hemoglobin A1c. Routine blood will be collected as regular standard of care with each visit. MMA will also be assessed. Peripheral serum values (CBC, B12) will serve as a representation of central micronutrient availability * Clinical Evaluation: the Newcastle mitochondrial disease adult scale (NMDAS) | Dietary supplement | – |
Primary outcome
Macrocytosis
Time frame: 1 year
• Proportion of patients who normalize their MCV (measured in fL) such that the MCV Is within the normal range of the testing laboratory after 6 months of vitamin therapy
1 secondary outcome
Newcastle mitochondrial disease adult scale (NMDAS)
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Folinic acid (oral); Cyanocobalamin sublingual in people with Mitochondrial DNA Deletion and Macrocytosis, run by University of British Columbia.
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: status not confirmed, as of the sponsor's last update on 29 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Macrocytosis (time frame: 1 year). 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 29 Dec 2023; AzTrials last refreshed its copy on 8 Nov 2026.