Familial DysautonomiaPhase 2NCT02276716
The Nutritional Supplement Phosphatidylserine in Patients With Familial Dysautonomia
A Phase 2 study testing Phosphatidylserine in people with Familial Dysautonomia, run by NYU Langone Health at 1 site in United States.
Trial summary
Familial dysautonomia (FD) is a devastating hereditary disease in which the development of selective neuronal populations is impaired because of a deficiency of the protein IKAP (Slaugenhaupt, 2002). There is no known cure. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Familial Dysautonomia
- What is being tested?
- Phosphatidylserine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2011to 1 Aug 2019
- Phase
- Phase 2
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- - Diagnosis of familial dysautonomia (with mutation testing)
- Age 12 years or older
- Signed informed consent (or ascent), which will include permission to assess medical records
Who cannot join
- Patients with significant cardiac, respiratory, or renal compromise that, in the investigators opinion, may jeopardize their health by participating in this trial
- Patients who are currently participating in other clinical trials of compounds that my change IKAP gene expression.
- Women who are pregnant or lactating
- Women of childbearing potential who are not using medically accepted methods of contraception.
- Patients taking anticoagulants, such as warfarin, heparin, aspirin, pentoxifylline, clopidogrel or ticlopidine.
- Patients taking ginko, garlic or vitamin E supplements.
Trial locations and contacts
1 site in 1 country.
United States1 site
NYU Langone Medical Center, Dyautonomia Center, Suite 9Q
New York, New York, 10016
About this study
Official title: The Nutritional Supplement Phosphatidylserine in Patients With Familial
Familial dysautonomia (FD) is a devastating hereditary disease in which the development of selective neuronal populations is impaired because of a deficiency of the protein IKAP (Slaugenhaupt, 2002). There is no known cure. Treatments are supportive, often ineffective and around half of all patients die before reaching age 40 (Axelrod et al., 2002).
Phosphatidylserine is an FDA approved food supplement that was shown recently to correct the genetic abnormality and restore IKAP protein levels in cell lines derived from patients with FD (Keren et al., 2011) and a humanized mouse model of the disease (Bochner et al., 2013). Despite its safety and efficacy in this fragile population being unknown, many patients with FD are currently taking phosphatidylserine
Read more
The investigators propose to conduct a safety, tolerability and early proof of concept efficacy study of phosphatidylserine in patients with FD. The study will be divided into two independent arms. The first phase of the study will be an open-label dose titration study to determine the safety and optimal dose of phosphatidylserine and its effect of normal IKBKAP mRNA levels in 40 patients with FD. The second phase will be a longitudinal observational study in which we will follow, on a yearly basis, patients with FD of all ages who opt to take phosphatidylserine. In this study, we will evaluate the long-term safety of phosphatidylserine in patients with FD and hope to determine whether phosphatidylserine has any impact on the clinical evolution of the disorder.
Our long-term goal is to find an effective therapy that will improve the quality of life for patients with FD and alter disease prognosis. We believe that the promise of phosphatidylserine and its availability in health food shops warrants a controlled safety, tolerability and efficacy study to determine whether it should be taken by patients with FD. This study is not intended to determine whether phosphatidylserine has a new indication to treat FD.
Read the detailed description
Familial dysautonomia (FD) is an autosomal recessive disease caused by mutations in the I-B kinase complex associated protein (IKBKAP) gene sequence (Anderson et al., 2001; Slaugenhaupt et al., 2001). The disorder affects the development of sensory nerves, resulting in impaired pain and temperature perception (Riley et al., 1949), lack of visceral sensations (Norcliffe-Kaufmann et al., 2010), dysphagia and proprioceptive gait ataxia (Macefield et al., 2011). Childhood mortality is increased, with aspiration pneumonia a leading cause of death. In early adulthood, renal failure is common (Pearson et al., 1980) and eyesight deteriorates due to optic atrophy and gait ataxia worsens making walking impossible without assistance. The incidence of seizures, scoliosis, respiratory insufficiency, sleep apnea and gastrointestinal bleeds are all increased. Sudden unexpected cardiac deaths are common and there is an increased incidence of cancer. Current treatments are supportive and frequently ineffective. FD has no known cure and 50% of patients die before age 40.
A decade ago, we discovered that the disease was caused by point mutations in IKBKAP gene, leading to a deficiency of I-B kinase complex associated protein (IKAP) mainly in neuronal tissue (Slaugenhaupt et al., 2001; Mezey et al., 2003; Lee et al., 2009). Phosphatidylserine, an FDA-approved food supplement, was shown to increase protein levels in FD-derived cell lines (Keren et al., 2011) as well as in a mouse model of FD (Bochner et al., 2013). Because of the severity of FD, the availability of phosphatidylserine in health food stores and its promise as a treatment, many patients with FD are already taking it, although its safety and efficacy in this population is unknown. Thus, we propose a controlled study of phosphatidylserine to determine its safety profile and whether it has any impact on the natural history of FD.
SPECIFIC AIM 1: It is not known if phosphatidylserine increases the levels of IKBKAP mRNA in patients with FD. To determine the optimal dose of phosphatidylserine in patients with FD, (i.e., the lowest dosage at which there is maximal improvement in IKBKAP mRNA production without significant side effects) we will monitor the safety and efficacy of phosphatidylserine in an open-label dose escalation study. Safety parameters and IKBKAP mRNA levels in blood will be measured in 40 patients with FD at baseline and repeated at increasing doses of phosphatidylserine.
SPECIFIC AIM 2: In an independent long-term observational study, we will follow patients with FD of all ages who opt to take phosphatidylserine as a food supplement in their diet. Safety parameters will be measured as part of routine evaluations on an annual basis. The long-term efficacy of phosphatidylserine will be determined by evaluating the evolution of standard parameters of neurological function overtime in patients who received phosphatidylserine and comparing their progression with historical controls from the database archives.
- Conditions
- Familial Dysautonomia
- Being tested
- Phosphatidylserine
- Medical subject headings
- Dysautonomia, Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhosphatidylserineDietary supplement
Phosphatidylserine will be titrated starting at 300mg/day dose for two months to 600mg/day dose for 2 months, then 800 mg/day dose for a final 2 month period.
| Study group | Role | What they receive |
|---|---|---|
| Phosphatidylserine | Experimental | Phosphatidylserine titration from 300, 600 and 800 mg/day
duration: 6 months Receives: Dietary Supplement: Phosphatidylserine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in blood lab values at every 2 month interval
blood lab values, CBC, metabolic panel,physical exam, vital signs, 12 lead ECG
Measured: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
Change from baseline in adverse events measures at every 2 month interval
number of participants with adverse events
Measured: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
Change from baseline in physical exam measures at every 2 month interval
change from baseline in physical exam
Measured: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
Change from baseline in 12 lead ECG measures at every 2 month interval
change from baseline in 12 lead ECG
Measured: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
Change from baseline in vital signs measures at every 2 month interval
change from baseline in sitting blood pressure, body temperature
Measured: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
Secondary outcomes (1)
Change from baseline in efficacy measures
Change from baseline in IKBKP mRNA blood levels at each 2 month intervals
Measured: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2014 (estimated)
- Study startNov 2011
- Primary completion1 Aug 2019
- Study completion1 Aug 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Familial DysautonomiaStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Horacio Kaufmann, MD, Principal investigator, NYU School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02276716
- Sponsor's protocol ID
- 11-02100
- Status last verified
- Feb 2021
- First submitted
- 16 Oct 2014
- Last updated
- 21 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Nutritional Supplement Phosphatidylserine in Patients With Familial
- ClinicalTrials.gov ID
- NCT02276716
- Acronym / sponsor ID
- 11-02100
- Conditions
- Familial Dysautonomia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Nov 2011
- Primary completion
- 1 Aug 2019 (actual)
- Study completion
- 1 Aug 2019 (actual)
- First posted
- 28 Oct 2014 (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.
Familial dysautonomia (FD) is a devastating hereditary disease in which the development of selective neuronal populations is impaired because of a deficiency of the protein IKAP (Slaugenhaupt, 2002). There is no known cure. Treatments are supportive, often ineffective and around half of all patients die before reaching age 40 (Axelrod et al., 2002).
Phosphatidylserine is an FDA approved food supplement that was shown recently to correct the genetic abnormality and restore IKAP protein levels in cell lines derived from patients with FD (Keren et al., 2011) and a humanized mouse model of the disease (Bochner et al., 2013). Despite its safety and efficacy in this fragile population being unknown, many patients with FD are currently taking phosphatidylserine
The investigators propose to conduct a safety, tolerability and early proof of concept efficacy study of phosphatidylserine in patients with FD. The study will be divided into two independent arms. The first phase of the study will be an open-label dose titration study to determine the safety and optimal dose of phosphatidylserine and its effect of normal IKBKAP mRNA levels in 40 patients with FD. The second phase will be a longitudinal observational study in which we will follow, on a yearly basis, patients with FD of all ages who opt to take phosphatidylserine. In this study, we will evaluate the long-term safety of phosphatidylserine in patients with FD and hope to determine whether phosphatidylserine has any impact on the clinical evolution of the disorder.
Our long-term goal is to find an effective therapy that will improve the quality of life for patients with FD and alter disease prognosis. We believe that the promise of phosphatidylserine and its availability in health food shops warrants a controlled safety, tolerability and efficacy study to determine whether it should be taken by patients with FD. This study is not intended to determine whether phosphatidylserine has a new indication to treat FD.
Detailed description
Familial dysautonomia (FD) is an autosomal recessive disease caused by mutations in the I-B kinase complex associated protein (IKBKAP) gene sequence (Anderson et al., 2001; Slaugenhaupt et al., 2001). The disorder affects the development of sensory nerves, resulting in impaired pain and temperature perception (Riley et al., 1949), lack of visceral sensations (Norcliffe-Kaufmann et al., 2010), dysphagia and proprioceptive gait ataxia (Macefield et al., 2011). Childhood mortality is increased, with aspiration pneumonia a leading cause of death. In early adulthood, renal failure is common (Pearson et al., 1980) and eyesight deteriorates due to optic atrophy and gait ataxia worsens making walking impossible without assistance. The incidence of seizures, scoliosis, respiratory insufficiency, sleep apnea and gastrointestinal bleeds are all increased. Sudden unexpected cardiac deaths are common and there is an increased incidence of cancer. Current treatments are supportive and frequently ineffective. FD has no known cure and 50% of patients die before age 40.
A decade ago, we discovered that the disease was caused by point mutations in IKBKAP gene, leading to a deficiency of I-B kinase complex associated protein (IKAP) mainly in neuronal tissue (Slaugenhaupt et al., 2001; Mezey et al., 2003; Lee et al., 2009). Phosphatidylserine, an FDA-approved food supplement, was shown to increase protein levels in FD-derived cell lines (Keren et al., 2011) as well as in a mouse model of FD (Bochner et al., 2013). Because of the severity of FD, the availability of phosphatidylserine in health food stores and its promise as a treatment, many patients with FD are already taking it, although its safety and efficacy in this population is unknown. Thus, we propose a controlled study of phosphatidylserine to determine its safety profile and whether it has any impact on the natural history of FD.
SPECIFIC AIM 1: It is not known if phosphatidylserine increases the levels of IKBKAP mRNA in patients with FD. To determine the optimal dose of phosphatidylserine in patients with FD, (i.e., the lowest dosage at which there is maximal improvement in IKBKAP mRNA production without significant side effects) we will monitor the safety and efficacy of phosphatidylserine in an open-label dose escalation study. Safety parameters and IKBKAP mRNA levels in blood will be measured in 40 patients with FD at baseline and repeated at increasing doses of phosphatidylserine.
SPECIFIC AIM 2: In an independent long-term observational study, we will follow patients with FD of all ages who opt to take phosphatidylserine as a food supplement in their diet. Safety parameters will be measured as part of routine evaluations on an annual basis. The long-term efficacy of phosphatidylserine will be determined by evaluating the evolution of standard parameters of neurological function overtime in patients who received phosphatidylserine and comparing their progression with historical controls from the database archives.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Phosphatidylserine | Experimental | Dietary Supplement: PhosphatidylserinePhosphatidylserine titration from 300, 600 and 800 mg/day duration: 6 months |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- - Diagnosis of familial dysautonomia (with mutation testing)
- Age 12 years or older
- Signed informed consent (or ascent), which will include permission to assess medical records
Key exclusion criteria (6 listed)
- Patients with significant cardiac, respiratory, or renal compromise that, in the investigators opinion, may jeopardize their health by participating in this trial
- Patients who are currently participating in other clinical trials of compounds that my change IKAP gene expression.
- Women who are pregnant or lactating
- Women of childbearing potential who are not using medically accepted methods of contraception.
- Patients taking anticoagulants, such as warfarin, heparin, aspirin, pentoxifylline, clopidogrel or ticlopidine.
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 |
|---|---|---|
| PhosphatidylserinePhosphatidylserine will be titrated starting at 300mg/day dose for two months to 600mg/day dose for 2 months, then 800 mg/day dose for a final 2 month period. | Dietary supplement | Phosphatidylserine |
Primary outcome
Change from baseline in blood lab values at every 2 month interval
Time frame: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
blood lab values, CBC, metabolic panel,physical exam, vital signs, 12 lead ECG
Change from baseline in adverse events measures at every 2 month interval
Time frame: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
number of participants with adverse events
Change from baseline in physical exam measures at every 2 month interval
Time frame: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
change from baseline in physical exam
Change from baseline in 12 lead ECG measures at every 2 month interval
Time frame: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
change from baseline in 12 lead ECG
Change from baseline in vital signs measures at every 2 month interval
Time frame: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
change from baseline in sitting blood pressure, body temperature
1 secondary outcome
Change from baseline in efficacy measures
Time frame: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years
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 21 Feb 2021.
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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.
Horacio Kaufmann, MD principal investigator
NYU School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Phosphatidylserine in people with Familial Dysautonomia, run by NYU Langone Health 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 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: finished, as of the sponsor's last update on 21 Feb 2021. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Change from baseline in blood lab values at every 2 month interval (time frame: measurements will be taken at baseline and at two months intervals for the first 6 months, then at yearly intervals for up to 5 years). The study lists 5 primary outcomes in all. 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 21 Feb 2021.