The Safety and Tolerability of Kinetin, in Patients With Familial Dysautonomia

NCT02274051 | Completed Phase 1

• 1 other identifier: 09-0762
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study of kinetin, a nutritional supplement that corrects the mRNA splicing defect in patients with familial dysautonomia (FD, also known as Riley Day syndrome or hereditary sensory and autonomic neuropathy type III). FD is a rare fatal autosomal recessive disease in which the growth and development of selective neuronal populations is impaired. The disease is the result of a point mutation in the gene sequence that encodes for kinase complex associated protein (IKAP) in chromosome 9q31. The mutation, at the start of the non-encoding intron 20, weakens the splice site, causing the spliceosome to wrongly join together exons 19 and 21 when transcribing the mRNA strand and miss out exon 20. The mutated mRNA produces a short unstable IKAP protein that is quickly degraded. Interestingly, the mutation does not lead to a complete loss of function. Instead, it results in a tissue specific deficiency in splicing efficiency with both normal (wild type) and mutant IKAP mRNA being expressed in different ratios in different tissues. Some cells, like fibroblasts, produce mostly normal mRNA and protein, where as others, like neurons, produce mostly mutant mRNA and almost no functional protein product.

Conditions

Familial Dysautonomia

Outcome Measures

Primary Outcomes (4)

• Change in Safety blood labs

  safety blood labs (CBC, metabolic panel)

  At baseline and after each 6 months period and at 36 months

• Change in vital signs

  Sitting and standing blood pressure measurements and heart rate

  At baseline and after each 6 months period and at 36 months

• Change in ECG

  12 lead ECG measures

  At baseline and after each 6 months period and at 36 months

• Number of participants with adverse events

  Number of adverse events

  At baseline and after each 6 months period and at 36 months

Study Arms (1)

Kinetin

EXPERIMENTAL

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

Interventions

Kinetin DIETARY_SUPPLEMENT

Titration of Kinetin to maximum individualized dose, then steady state over a 3 year period once daily dose.

Kinetin

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male of female patients aged 16 and older
• Confirmed diagnosis of familial dysautonomia by genetic testing
• Written informed consent to participate in the trial and understanding that they can withdraw consent at anytime without affecting their future care.
• Ability to comply with the requirements of the study procedures.

You may not qualify if:

• Patients who have taken other nutritional supplements that may affect IKAP mRNA splicing within the last 30 days
• Patients with a known hypersensitivity to any component of the nutritional supplement kinetin
• Patients with atrial fibrillation, angina or an electrocardiogram documenting significant abnormality that may jeopardize the patient's health.
• Patients with significant pulmonary, liver, renal (creatinine \>2.5 mg/ml) or cardiac illness
• Women who are pregnant or lactating
• Women of childbearing potential who are not using medically accepted methods of contraception.
• Patients who have a significant abnormality on clinical examination that may, in the investigator's opinion, jeopardize their healthy participating in this pilot trial.
• Patients taking allopurinol, other xanthine oxidase inhibitors or other compounds that may interfere with the metabolism of kinetin including oral calcium supplements.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Medical Center

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Dysautonomia, Familial

Interventions

Kinetin

Condition Hierarchy (Ancestors)

Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Hereditary Sensory and Autonomic Neuropathies; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Cytokinins; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Horacio Kaufmann, MD

  NYU School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: October 24, 2014
• Study Start: November 1, 2009
• Primary Completion: May 4, 2019
• Study Completion: May 4, 2019
• Last Updated: June 18, 2019

Record last verified: 2019-06

Locations

US (1)