The Safety and Tolerability of Kinetin, in Patients With Familial Dysautonomia
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|ClinicalTrials.gov Identifier: NCT02274051|
Recruitment Status : Completed
First Posted : October 24, 2014
Last Update Posted : June 18, 2019
|Condition or disease||Intervention/treatment||Phase|
|Familial Dysautonomia||Dietary Supplement: Kinetin||Phase 1|
Familial dysautonomia (FD, also called Riley Day syndrome or hereditary sensory and autonomic neuropathy type III) is an autosomal recessive disease caused by a point mutation in the kinase complex associated protein (IKAP) gene sequence (1, 2). This leads to a tissue specific splicing defect with variable "skipping" of exon 20 (1, 3, 4). The consequence is a devastating congenital sensory neuropathy, affecting pain and temperature perception (5) as well as afferent information from the viscera (6). As a result, patients suffer recurrent aspiration pneumonias, respiratory insufficiency, proprioceptive ataxia, scoliosis and the long-term consequences of volatile blood pressure including renal failure (7) and left ventricular hypertrophy (8).
In-vitro studies have shown that the plant hormone kinetin corrects the splicing defect and increases the production of normal IKAP protein levels in FD derived cell lines (9, 10). Preliminary studies in heterozygous carriers of the IKAP mutation showed that dietary supplementation with kinetin increased the production of correctly spliced IKAP mRNA, in white blood cells (11). Preliminary studies in patients with FD have demonstrated that kinetin also increases the expression of correctly spliced IKAP mRNA extracted from white blood cells. However, the effect of kinetin on mRNA levels in neuronal tissue is unknown.
The overall objective of this study is to assess the safety and tolerability of administering kinetin in patients with FD. The specific aim of this proposal is to determine the safety of a once daily dose of kinetin in patients with FD using a dose ascending titration and to determine the long-term safety and tolerability during 3-years of receiving a maximum tolerated steady state dose of kinetin. The investigators hope to also demonstrate early proof of concept that kinetin enhances the ability of neuronal tissue to correctly splice IKAP mRNA.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Safety and Tolerability of Kinetin, a Nutritional Supplement That Corrects the Splicing Defect, in Patients With Familial Dysautonomia|
|Study Start Date :||November 2009|
|Actual Primary Completion Date :||May 4, 2019|
|Actual Study Completion Date :||May 4, 2019|
Kinetin titration phase to 30mg/kg dose or individual max dose taken once daily.
Patients will then proceed to steady state long-term phase at maximum individual dose of kinetin over a 3 year period.
Dietary Supplement: Kinetin
Titration of Kinetin to maximum individualized dose, then steady state over a 3 year period once daily dose.
- Change in Safety blood labs [ Time Frame: At baseline and after each 6 months period and at 36 months ]safety blood labs (CBC, metabolic panel)
- Change in vital signs [ Time Frame: At baseline and after each 6 months period and at 36 months ]Sitting and standing blood pressure measurements and heart rate
- Change in ECG [ Time Frame: At baseline and after each 6 months period and at 36 months ]12 lead ECG measures
- Number of participants with adverse events [ Time Frame: At baseline and after each 6 months period and at 36 months ]Number of adverse events
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02274051
|United States, New York|
|NYU Langone Medical Center|
|New York, New York, United States, 10016|
|Principal Investigator:||Horacio Kaufmann, MD||NYU School of Medicine|