Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02276716 |
| Other study ID # |
11-02100 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
November 2011 |
| Est. completion date |
August 1, 2019 |
Study information
| Verified date |
February 2021 |
| Source |
NYU Langone Health |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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. 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.
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.
