Mitochondrial DiseasesNCT02809170
The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
A study testing Arginine and Citrulline in people with Mitochondrial Diseases, run by Tawam Hospital at 1 site in United Arab Emirates.
Trial summary
Mitochondrial diseases occur due to inadequate energy production. In addition, nitric oxide (NO) deficiency occurs in mitochondrial diseases. The endothelial layer of blood vessels functions in maintaining blood vessels patency through producing NO which relaxes vascular smooth muscles and therefore maintains the… Read more about this study
- Who is it for?
- Ages 3 to 18 yearsHealthy volunteers can take part
- Conditions the study is for
- Mitochondrial Diseases
- What is being tested?
- Arginine and Citrulline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited Arab Emirates
- Study dates
- Jun 2016to Jun 2019
- Phase
- Interventional
- 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 3 to 18 years
- All sexes
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- Diagnosis of mitochondrial disease with multi-organ disease involving neurological and/or muscular systems.
- The diagnosis must be confirmed either molecularly (identifying mutations known to be associated with mitochondrial diseases) or by respiratory chain assay abnormalities.
Who cannot join
- Have acute illness or physical disability interfering with ability to undergo the study procedures.
- Known to have other factors that are known to result in endothelial dysfunction including hypertension, hyperlipidemia, and diabetes.
Trial locations and contacts
1 site in 1 country.
About this study
Mitochondrial diseases occur due to inadequate energy production. In addition, nitric oxide (NO) deficiency occurs in mitochondrial diseases. The endothelial layer of blood vessels functions in maintaining blood vessels patency through producing NO which relaxes vascular smooth muscles and therefore maintains the patency of blood vessels and adequate blood perfusion. In mitochondrial diseases, endothelial cells fail to perform their normal function in maintaining the patency of blood vessels (endothelial dysfunction) because of the inability to produce enough NO. Endothelial dysfunction results in decreased blood perfusion in different organs which can contribute to the complications seen in mitochondrial diseases. The amino acids arginine and citrulline act as NO precursors and can increase NO production. In this study we hypothesize that due to the inability to produce enough NO patients with mitochondrial diseases have endothelial dysfunction that will improve after arginine or citrulline supplementation. The investigators will assess endothelial function using peripheral arterial tonometry before and after arginine or citrulline supplementation. The investigators expect that arginine and citrulline supplementation will improve endothelium function. This will support the therapeutic use of arginine and citrulline in mitochondrial diseases.
Read the detailed description
The investigators will study 10 children with mitochondrial diseases and 10 healthy control children. The investigators will study control children to be able compare the results of children with mitochondrial diseases to control healthy children. Therefore, the investigators will study control children only once to compare these results to the results of children with mitochondrial diseases at baseline. To assess the effect of arginine and citrulline on children with mitochondrial diseases, the investigators need to assess children with mitochondrial diseases four times. First time as baseline. Then children with mitochondrial diseases will be randomized to receive either oral arginine or citrulline at a dose of 500 mg/kg/day divided in 3 doses daily for 2 weeks after which a second assessment will be performed. Oral arginine or citrulline will be discontinued and after a two-week washout period another baseline assessment will be done. After that, the child will be started on oral citrulline (if the participant received arginine the first time) or arginine (if the participant received citrulline the first time) at a dose of 500 mg/kg/day divided in 3 doses daily for 2 weeks after which a fourth assessment will be done.
- Conditions
- Mitochondrial Diseases
- Being tested
- Arginine, Citrulline
- Medical subject headings
- Mitochondrial Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ArginineDietary supplement
Arginine is an amino acids
CitrullineDietary supplement
Citrulline is an amino acid
| Study group | Role | What they receive |
|---|---|---|
| Arginine | Active comparator | Endothelial function will be assessed before and after arginine supplementation Receives: Dietary Supplement: Arginine |
| Citrulline | Active comparator | Endothelial function will be assessed before and after citrulline supplementation Receives: Dietary Supplement: Citrulline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reactive hyperemic index (RHI)
Reactive hyperemic index (RHI) which reflects endothelial function will be measured using the EndoPAT instrument
Measured: 2 year
Secondary outcomes (1)
Plasma concentration levels of arginine and citrulline
Plasma arginine and citrulline levels will also be measured
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2016 (estimated)
- Study startJun 2016
- Primary completionJun 2019
- Study completionJun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitochondrial DiseasesStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tawam Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ayman El-Hattab, Tawam Hospital
- Investigators
- Ayman W El-Hattab, MD, Principal investigator, Tawam Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02809170
- Sponsor's protocol ID
- CED 343-14
- Status last verified
- Mar 2020
- First submitted
- 15 Jun 2016
- Last updated
- 18 Mar 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Arginine and Citrulline Supplementation on Endothelial Dysfunction in Mitochondrial Diseases
- ClinicalTrials.gov ID
- NCT02809170
- Acronym / sponsor ID
- CED 343-14
- Conditions
- Mitochondrial Diseases
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Tawam HospitalUniversity, hospital or other
- Study start
- Jun 2016
- Primary completion
- Jun 2019 (actual)
- Study completion
- Jun 2019 (actual)
- First posted
- 22 Jun 2016 (estimated)
- 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.
Mitochondrial diseases occur due to inadequate energy production. In addition, nitric oxide (NO) deficiency occurs in mitochondrial diseases. The endothelial layer of blood vessels functions in maintaining blood vessels patency through producing NO which relaxes vascular smooth muscles and therefore maintains the patency of blood vessels and adequate blood perfusion. In mitochondrial diseases, endothelial cells fail to perform their normal function in maintaining the patency of blood vessels (endothelial dysfunction) because of the inability to produce enough NO. Endothelial dysfunction results in decreased blood perfusion in different organs which can contribute to the complications seen in mitochondrial diseases. The amino acids arginine and citrulline act as NO precursors and can increase NO production. In this study we hypothesize that due to the inability to produce enough NO patients with mitochondrial diseases have endothelial dysfunction that will improve after arginine or citrulline supplementation. The investigators will assess endothelial function using peripheral arterial tonometry before and after arginine or citrulline supplementation. The investigators expect that arginine and citrulline supplementation will improve endothelium function. This will support the therapeutic use of arginine and citrulline in mitochondrial diseases.
Detailed description
The investigators will study 10 children with mitochondrial diseases and 10 healthy control children. The investigators will study control children to be able compare the results of children with mitochondrial diseases to control healthy children. Therefore, the investigators will study control children only once to compare these results to the results of children with mitochondrial diseases at baseline. To assess the effect of arginine and citrulline on children with mitochondrial diseases, the investigators need to assess children with mitochondrial diseases four times. First time as baseline. Then children with mitochondrial diseases will be randomized to receive either oral arginine or citrulline at a dose of 500 mg/kg/day divided in 3 doses daily for 2 weeks after which a second assessment will be performed. Oral arginine or citrulline will be discontinued and after a two-week washout period another baseline assessment will be done. After that, the child will be started on oral citrulline (if the participant received arginine the first time) or arginine (if the participant received citrulline the first time) at a dose of 500 mg/kg/day divided in 3 doses daily for 2 weeks after which a fourth assessment will be done.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arginine | Active comparator | Dietary Supplement: ArginineEndothelial function will be assessed before and after arginine supplementation |
| Citrulline | Active comparator | Dietary Supplement: CitrullineEndothelial function will be assessed before and after citrulline supplementation |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Diagnosis of mitochondrial disease with multi-organ disease involving neurological and/or muscular systems.
- The diagnosis must be confirmed either molecularly (identifying mutations known to be associated with mitochondrial diseases) or by respiratory chain assay abnormalities.
Key exclusion criteria (2 listed)
- Have acute illness or physical disability interfering with ability to undergo the study procedures.
- Known to have other factors that are known to result in endothelial dysfunction including hypertension, hyperlipidemia, and diabetes.
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 |
|---|---|---|
| ArginineArginine is an amino acids | Dietary supplement | Arginine |
| CitrullineCitrulline is an amino acid | Dietary supplement | Citrulline |
Primary outcome
Reactive hyperemic index (RHI)
Time frame: 2 year
Reactive hyperemic index (RHI) which reflects endothelial function will be measured using the EndoPAT instrument
1 secondary outcome
Plasma concentration levels of arginine and citrulline
Time frame: 2 year
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 18 Mar 2020.
- Individual participant dataSharing planned: Yes
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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.
Ayman W El-Hattab, MD principal investigator
Tawam Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Arginine and Citrulline in people with Mitochondrial Diseases, run by Tawam Hospital at 1 site in United Arab Emirates.
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 2 inclusion and 2 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 18 Mar 2020. 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 Arab Emirates. 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?
Reactive hyperemic index (RHI) (time frame: 2 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 18 Mar 2020.