Familial DysautonomiaPhase 1NCT02274051
The Safety and Tolerability of Kinetin, in Patients With Familial Dysautonomia
A Phase 1 study testing Kinetin in people with Familial Dysautonomia, run by NYU Langone Health at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Familial Dysautonomia
- What is being tested?
- Kinetin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2009to 4 May 2019
- Phase
- Phase 1
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
NYU Langone Medical Center
New York, New York, 10016
About this study
Official title: The Safety and Tolerability of Kinetin, a Nutritional Supplement That Corrects the Splicing Defect, in Patients With Familial Dysautonomia
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.
Read the detailed description
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.
- Conditions
- Familial Dysautonomia
- Being tested
- Kinetin
- Medical subject headings
- Dysautonomia, Familial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KinetinDietary supplement
Titration of Kinetin to maximum individualized dose, then steady state over a 3 year period once daily dose.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Dietary Supplement: Kinetin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Safety blood labs
safety blood labs (CBC, metabolic panel)
Measured: 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
Measured: At baseline and after each 6 months period and at 36 months
Change in ECG
12 lead ECG measures
Measured: At baseline and after each 6 months period and at 36 months
Number of participants with adverse events
Number of adverse events
Measured: At baseline and after each 6 months period and at 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2014 (estimated)
- Study startNov 2009
- Primary completion4 May 2019
- Study completion4 May 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 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
- NCT02274051
- Sponsor's protocol ID
- 09-0762
- Status last verified
- Jun 2019
- First submitted
- 21 Oct 2014
- Last updated
- 18 Jun 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety and Tolerability of Kinetin, a Nutritional Supplement That Corrects the Splicing Defect, in Patients With Familial Dysautonomia
- ClinicalTrials.gov ID
- NCT02274051
- Acronym / sponsor ID
- 09-0762
- Conditions
- Familial Dysautonomia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Nov 2009
- Primary completion
- 4 May 2019 (actual)
- Study completion
- 4 May 2019 (actual)
- First posted
- 24 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.
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.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Kinetin | Experimental | Dietary Supplement: KinetinKinetin 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. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
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 |
|---|---|---|
| KinetinTitration of Kinetin to maximum individualized dose, then steady state over a 3 year period once daily dose. | Dietary supplement | Kinetin |
Primary outcome
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
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 18 Jun 2019.
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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 1 study testing Kinetin 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 4 inclusion and 8 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 18 Jun 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 in Safety blood labs (time frame: At baseline and after each 6 months period and at 36 months). The study lists 4 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 18 Jun 2019.