Acidosis, LacticNCT00031161
Prevention of Dichloroacetate Toxicity
A study testing Nitisinone (NTBC), Dichloroacetate and Low-tyrosin diet in people with Acidosis, Lactic and Chronic Disease, run by University of Florida at 1 site in United States.
Trial summary
This is a study to determine the safety of dichloroacetate (DCA) with a low-tyrosine diet given with or without nitisinone (NTBC) in children with chronic lactic acidosis (CLA). Read more about this study
- Who is it for?
- Ages 3 months to 21 years
- Conditions the study is for
- Acidosis, Lactic, Chronic Disease
- What is being tested?
- Nitisinone (NTBC), Dichloroacetate and Low-tyrosin diet
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2001to Sep 2005
- 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 months to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Biochemical or molecular genetic proof of a defect in mitochondrial enzyme of glucose metabolism or oxidative phosphorylation.
- Clinical history consistent with CLA (e.g., basal hyperlactatemia, stroke-like episodes, neuromuscular degeneration, and seizures).
- Ability to withstand an 8-hour fast (if 2 years old or younger) or a 12-hour fast without developing hypoglycemia (blood glucose greater than or equal to 50 mg/dL).
Who cannot join
- Secondary lactic acidosis due to impaired oxygenation or circulation.
- Hyperlactatemia associated with proven biotinidase deficiency or with enzyme deficiencies of gluconeogenesis.
- Primary, defined organic acidurias other than lactic acidosis for which effective therapy is available (e.g., propionic aciduria).
- Primary disorders of amino acid metabolism.
- Primary disorders of fatty acid oxidation.
- Malabsorption syndromes associated with D-lactic acidosis.
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- Renal insufficiency.
- Serum creatinine greater than 1.2 mg/g.
- Creatinine clearance less than or equal to 60 mL/min.
- Primary hepatic disease unrelated to chronic lactic acidosis.
- In patients with pyruvate dehydrogenase enzyme complex deficiency, an inability to maintain a diet greater than 50% calories from fat without biological and/or neurological deterioration.
Trial locations and contacts
1 site in 1 country.
About this study
This is a study to determine the safety of dichloroacetate (DCA) with a low-tyrosine diet given with or without nitisinone (NTBC) in children with chronic lactic acidosis (CLA).
Read the detailed description
DCA is being studied for the treatment of patients with CLA, which is a rare collection of mitochondrial metabolism errors causing cellular energy failure and early death. DCA causes reversible liver and peripheral nerve toxicity and it interrupts both tyrosine and heme metabolism. The inhibitory effect of DCA on mammalian tyrosine metabolism elicits biochemical changes similar to those observed in hereditary tyrosinemia type I (HT). However, some reports and studies indicate substantial reduction in the biochemical and clinical consequences of HT may occur when patients are treated concomitantly with a low-tyrosine diet (LTD) and the chemical NTBC, which inhibits an early step in tyrosine catabolism. Possibly, the same dietary and pharmacologic interventions may mitigate or prevent toxicity associated with chronic DCA exposure.
Patients visit the Center 5 times over a 1-year period, usually for 2 to 3 days per visit, for an extensive series of clinical and biochemical tests. Visit 1 is for baseline examinations and blood and urine chemistries and to educate the patient on an LTD. This visit lasts approximately 7 days to determine acceptable circulating tyrosine concentrations for LTD formula at discharge. Patients are provided with tubes to take to local laboratories every 2 weeks for blood work. Patients are readmitted in 1 month to determine adherence to diet and serum tyrosine levels. Patients who evidence dietary compliance, no adverse effects, and a willingness to continue are placed in 1 of 2 treatment arms: DCA plus an LTD plus placebo or DCA plus an LTD plus NTBC. Thereafter, patients return during Months 5, 9, and 13, which completes their 1-year treatment phase.
Completion date provided represents the completion date of the grant per OOPD records
- Conditions
- Acidosis, Lactic, Chronic Disease
- Being tested
- Nitisinone (NTBC), Dichloroacetate, Low-tyrosin diet
- Keywords
- Tyrosine, Diet, 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, 4-Hydroxyphenylpyruvate Dioxygenase, Enzyme Inhibitors
- Medical subject headings
- Acidosis, Lactic, Chronic Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitisinone (NTBC)Drug
DichloroacetateDrug
Low-tyrosin dietBehavioural
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2002 (estimated)
- Study startSep 2001
- Study completionSep 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acidosis, LacticStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00031161
- Sponsor's protocol ID
- FD-R-2013-01
- Other IDs
- FD-R-002013-01
- Status last verified
- Jan 2002
- First submitted
- 26 Feb 2002
- Last updated
- 25 Mar 2015
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Dichloroacetate Toxicity
- ClinicalTrials.gov ID
- NCT00031161
- Acronym / sponsor ID
- FD-R-2013-01
- Conditions
- Acidosis, Lactic, Chronic Disease
- Keywords
- Tyrosine, Diet, 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione, 4-Hydroxyphenylpyruvate Dioxygenase, Enzyme Inhibitors
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Study start
- Sep 2001
- Study completion
- Sep 2005
- First posted
- 27 Feb 2002 (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.
This is a study to determine the safety of dichloroacetate (DCA) with a low-tyrosine diet given with or without nitisinone (NTBC) in children with chronic lactic acidosis (CLA).
Detailed description
DCA is being studied for the treatment of patients with CLA, which is a rare collection of mitochondrial metabolism errors causing cellular energy failure and early death. DCA causes reversible liver and peripheral nerve toxicity and it interrupts both tyrosine and heme metabolism. The inhibitory effect of DCA on mammalian tyrosine metabolism elicits biochemical changes similar to those observed in hereditary tyrosinemia type I (HT). However, some reports and studies indicate substantial reduction in the biochemical and clinical consequences of HT may occur when patients are treated concomitantly with a low-tyrosine diet (LTD) and the chemical NTBC, which inhibits an early step in tyrosine catabolism. Possibly, the same dietary and pharmacologic interventions may mitigate or prevent toxicity associated with chronic DCA exposure.
Patients visit the Center 5 times over a 1-year period, usually for 2 to 3 days per visit, for an extensive series of clinical and biochemical tests. Visit 1 is for baseline examinations and blood and urine chemistries and to educate the patient on an LTD. This visit lasts approximately 7 days to determine acceptable circulating tyrosine concentrations for LTD formula at discharge. Patients are provided with tubes to take to local laboratories every 2 weeks for blood work. Patients are readmitted in 1 month to determine adherence to diet and serum tyrosine levels. Patients who evidence dietary compliance, no adverse effects, and a willingness to continue are placed in 1 of 2 treatment arms: DCA plus an LTD plus placebo or DCA plus an LTD plus NTBC. Thereafter, patients return during Months 5, 9, and 13, which completes their 1-year treatment phase.
Completion date provided represents the completion date of the grant per OOPD records
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Masking
- Double blind
Who may qualify
- Ages
- 3 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Biochemical or molecular genetic proof of a defect in mitochondrial enzyme of glucose metabolism or oxidative phosphorylation.
- Clinical history consistent with CLA (e.g., basal hyperlactatemia, stroke-like episodes, neuromuscular degeneration, and seizures).
- Ability to withstand an 8-hour fast (if 2 years old or younger) or a 12-hour fast without developing hypoglycemia (blood glucose greater than or equal to 50 mg/dL).
Key exclusion criteria (11 listed)
- Secondary lactic acidosis due to impaired oxygenation or circulation.
- Hyperlactatemia associated with proven biotinidase deficiency or with enzyme deficiencies of gluconeogenesis.
- Primary, defined organic acidurias other than lactic acidosis for which effective therapy is available (e.g., propionic aciduria).
- Primary disorders of amino acid metabolism.
- Primary disorders of fatty acid oxidation.
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 |
|---|---|---|
| Nitisinone (NTBC) | Drug | – |
| Dichloroacetate | Drug | – |
| Low-tyrosin diet | Behavioural | – |
Primary outcome
Not reported in the source record.
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 25 Mar 2015.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nitisinone (NTBC), Dichloroacetate and Low-tyrosin diet in people with Acidosis, Lactic and Chronic Disease, run by University of Florida 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 3 inclusion and 11 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 25 Mar 2015. 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?
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.
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 25 Mar 2015.