To evaluate product acceptability, tolerance and adherence during an 8-week intake of PDE MAX in patients with Pyridoxine Dependent Epilepsy.To evaluate the effects on metabolic control by comparing the changes from baseline after an 8-week intake…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
- Inborn errors of metabolism
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To evaluate the product acceptability, tolerance and adherence during an 8-week
intake of PDE MAX in patients with Pyridoxine Dependent Epilepsy.
Secondary outcome
To observe the changes from baseline, after an 8-week intake of PDE MAX, in PDE
biomarkers:
• Pipecolic acid in plasma
• 6-oxo-pipecolic acid in bloodspot, plasma and urine
• P6C in plasma and bloodspot
• αAASA in plasma and urine
• Amino acid profile in plasma
• Whole blood serotonin
• Pyridoxal phosphate in plasma
• Vitamers in plasma
• Organic acids in urine
• 2OPP in bloodspot, plasma and urine
The outcome of this assessment will be used to support regulatory submissions
by Vitaflo (International) Ltd. for the purpose of registration in any
geography for sale and/or reimbursement of the product as appropriate.
Background summary
Pyridoxine dependent epilepsy (PDE) is a rare (~1:350,000), inherited disorder
characterised by recurrent and drug resistant seizures. The disorder is
pyridoxine (vitamin B6) dependent and patients are treated with high doses of
this, although they are not deficient. 75% of patients have intellectual
developmental disability and/or delay, despite adequate seizure control from
treatment. Best practice is for triple therapy: pyridoxine, arginine
supplementation and lysine restriction.
There is often delayed diagnosis. 6-oxo-pipecolic acid has been identified as a
novel biomarker that utilises current newborn screening techniques. Another
biomarker has also recently been discovered, 2OPP.
There is currently no protein substitute designed specifically for PDE.
Patients are being offered a *best fit* diet based on another condition,
Glutaric Aciduria Type 1 (GA1). The GA1 products are low in lysine but also low
in tryptophan, which may cause a deficiency for PDE patients. Due to the
restrictive nature of the low protein diet, PDE sufferers are also at an
increased risk of micronutrient deficiencies.
Therefore, vitamins, minerals and trace elements are incorporated into PDE MAX,
to adequately replace the micronutrients that would typically be consumed
through dietary protein intake.
The study will recruit up to 15 participants aged one and above to evaluate PDE
Max on acceptability and tolerance.
Study objective
To evaluate product acceptability, tolerance and adherence during an 8-week
intake of PDE MAX in patients with Pyridoxine Dependent Epilepsy.
To evaluate the effects on metabolic control by comparing the changes from
baseline after an 8-week intake of PDE MAX in the biomarkers described in the
secondary outcomes.
Study design
This is a prospective, feasibility study in up to 15 participants aged one (1)
year and over of PDE MAX for the dietary management of Pyridoxine Dependent
Epilepsy. Participants will be provided with an eight-week supply of PDE MAX
and will be asked to complete a daily diary and short questionnaire to record
information on the following:
• Adherence
• Gastrointestinal tolerance
• Palatability
• How the product is used
Blood and urine samples will be taken at the beginning and end of the study to
measure several biochemical parameters. Physical and neurological assessments
will be carried out by the local Metabolic Consultant at the beginning and end
of the study. Routine monitoring of lysine levels will continue.
Patients can then continue to use PDE Max if deemed desirable by the physician,
dietitian and patient. The patients will then be followed for 12 months
according to routine care and data on growth, lysine levels and diet
information will be collected to also assess use over the longer term.
Intervention
15 participants, aged one (1) year and above, will have a 3-day baseline period
on their current dietary regimen and then for the next 53 days will add PDE MAX
to their diet under the direction of a dietitian. Blood and urine samples will
be taken at baseline and the end of the study for biomarker analysis.
Participants or their parents/guardian will complete a daily diary on adherence
and seizures throughout the study and a GI symptoms diary in weeks 1, 4 and 8.
Study burden and risks
Results of this study will provide insight into the acceptability and tolerance
of PDE Max as part of the dietary treatment to improve the metabolic health of
people with PDE.
The risks of the measurements are low and little physical or mental discomfort
is expected. Expected side effects could include gastrointestinal disturbance
from consuming PDE MAX. Patients are already using other lysine-free protein
supplements, although these are not well adapted to the PDE disease. PDE Max
has a more adequate protein composition for this group of patients. This may
lead to better outcomes for the patients and makes it possible to prescribe
patients a more appropriate diet for PDE.
Sefton Street 182
Liverpool L3 4BQ
GB
Sefton Street 182
Liverpool L3 4BQ
GB
Listed location countries
Age
Inclusion criteria
i) Diagnosis of Pyridoxine Dependent Epilepsy (PDE), biochemically and/or
genetically confirmed.
ii) Males or females aged one (1) year and above. Any participant aged 16 years
and over at screening must have the capacity to consent for themselves.
iii) Currently following a lysine-restricted diet for a minimum of four (4)
weeks prior to screening.
iv) Willing to take the study product and follow advice given by the dietitian.
v) Willingly given, written, informed consent from patient or parent/guardian.
vi) Willingly given, written assent (if appropriate).
Exclusion criteria
i) Inability to comply with the study protocol, in the opinion of the
investigator.
ii) Use of additional macro/micronutrient supplements during the study period,
unless clinically indicated and prescribed by the investigator, such as but not
limited to arginine and pyridoxine. In which case, supplementation must have
started four (4) weeks prior to screening with no anticipated changes to
intakes during the study duration.
iii) Participants who are pregnant / breastfeeding at the start of the study or
planning to become pregnant during the study period. Participants of
child-bearing potential will be required to undergo pregnancy test prior to
enrolment.
N.B.: Participants who become pregnant unexpectedly during this study may, in
consultation with their doctor, continue on the study*s dietary product if they
wish but will not have any investigations that would not normally be carried
out during pregnancy.
iv) Allergy to any ingredient present in the study product.
v) Other concurrent medical or psychiatric conditions, which, in the opinion of
the Investigator, would place the subject at increased risk, preclude obtaining
voluntary consent/assent or compliance with required study procedures, or would
confound the objectives of the study.
vi) Is participating in any other interventional study and has received any
other investigational drug, product or device within 30 days prior to screening
or are taking part in a non-medication study which, in the opinion of the
investigator, would interfere with study compliance or outcome assessments.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | NCT04672226 |
| CCMO | NL75819.091.20 |