Clinical Trial: The Nutritional Supplement Phosphatidylserine in Patients With Familial Dysautonomia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: The Nutritional Supplement Phosphatidylserine in Patients With Familial

Brief 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, tolera

Detailed Summary:

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. Sponsor: New York University School of Medicine

Current 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


Original Primary Outcome: Same as current

Current 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 ]

Change from baseline in IKBKP mRNA blood levels at each 2 month intervals


Original Secondary Outcome: Same as current

Information By: New York University School of Medicine

Dates:
Date Received: October 16, 2014
Date Started: November 2011
Date Completion: December 2018
Last Updated: February 24, 2017
Last Verified: February 2017