Ignite Creation Date:
2024-05-05 @ 11:40 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00102596
Status:
COMPLETED
Last Update Posted:
2012-02-01
First Post:
2005-01-30
Brief Title:
Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
Sponsor:
National Institute of Neurological Disorders and Stroke NINDS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Clinical Trial Characterizing the Bioavailability of 1-Octanol in Adults With Ethanol-responsive Essential Tremor
Status:
COMPLETED
Status Verified Date:
2012-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
OVERVIEW
Essential tremor ET is a common movement disorder affecting 04 of the general population and up to 14 of people 65 years and older Response to medications such as beta blockers and primidone may be of benefit but are often accompanied by intolerable side effects Response to ethanol on the other hand has a roughly 80 chance of significant tremor reduction though daily use of this as a treatment has potentially serious medical social and legal consequences
The leading hypothesis for ET pathophysiology is an unmasking of spontaneous oscillations originating in neurons of the inferior olive Both ethanol and 1-octanol have been shown to reduce these spontaneous oscillations in an animal model of ET however 1-octanol does this at a dose much lower than that leading to intoxication suggesting in may be useful in the treatment of essential tremor Our initial studies with 1-octanol have shown it to be safe at dosages up to 64mgkg without signs of intoxication while at the same time showing benefit
OBJECTIVE
We plan to evaluate the efficacy of different 1-octanol formulations in humans based on accelerometry and spirography We will also evaluate drug and metabolite bioavailabilities using a high performance liquid chromatography HPLC detection method from plasma and urine samples
STUDY POPULATION
We will study adult subjects with ethanol-responsive Essential Tremor ET
DESIGN
This study is designed as a two-phase unblinded inpatient study of adults with ET receiving weight-adjusted oral dosages of 2 different formulations of 1-octanol in a crossover fashion Phase I of the study is designed to develop an octanol detection assay using HPLC Four subjects will receive daily escalating dosages 1-32 mgkg of a single 1-octanol formulation followed by a crossover trial of both formulations at a dosage of 64 mgkg Phase II will study 20 subjects receiving one of the two formulations at 64 mgkg on inpatient day 1 followed by a 24 hour period of close monitoring The second formulation will be given on day 3 and the patient will again undergo close monitoring for 24 hours
OUTCOME MEASURES
The primary outcome measures for the study will be efficacy based on tremor ratings from accelerometry and spirography Secondary outcome measures will be the determination of bioavailability pharmacodynamic and pharmacokinetic profiles of octanol 61864 and octanol 68751 and their metabolites
Essential tremor ET is a common movement disorder affecting 04 of the general population and up to 14 of people 65 years and older Response to medications such as beta blockers and primidone may be of benefit but are often accompanied by intolerable side effects Response to ethanol on the other hand has a roughly 80 chance of significant tremor reduction though daily use of this as a treatment has potentially serious medical social and legal consequences
The leading hypothesis for ET pathophysiology is an unmasking of spontaneous oscillations originating in neurons of the inferior olive Both ethanol and 1-octanol have been shown to reduce these spontaneous oscillations in an animal model of ET however 1-octanol does this at a dose much lower than that leading to intoxication suggesting in may be useful in the treatment of essential tremor Our initial studies with 1-octanol have shown it to be safe at dosages up to 64mgkg without signs of intoxication while at the same time showing benefit
OBJECTIVE
We plan to evaluate the efficacy of different 1-octanol formulations in humans based on accelerometry and spirography We will also evaluate drug and metabolite bioavailabilities using a high performance liquid chromatography HPLC detection method from plasma and urine samples
STUDY POPULATION
We will study adult subjects with ethanol-responsive Essential Tremor ET
DESIGN
This study is designed as a two-phase unblinded inpatient study of adults with ET receiving weight-adjusted oral dosages of 2 different formulations of 1-octanol in a crossover fashion Phase I of the study is designed to develop an octanol detection assay using HPLC Four subjects will receive daily escalating dosages 1-32 mgkg of a single 1-octanol formulation followed by a crossover trial of both formulations at a dosage of 64 mgkg Phase II will study 20 subjects receiving one of the two formulations at 64 mgkg on inpatient day 1 followed by a 24 hour period of close monitoring The second formulation will be given on day 3 and the patient will again undergo close monitoring for 24 hours
OUTCOME MEASURES
The primary outcome measures for the study will be efficacy based on tremor ratings from accelerometry and spirography Secondary outcome measures will be the determination of bioavailability pharmacodynamic and pharmacokinetic profiles of octanol 61864 and octanol 68751 and their metabolites
Detailed Description:
OVERVIEW
Essential tremor ET is a common movement disorder affecting 04 of the general population and up to 14 of people 65 years and older Response to medications such as beta blockers and primidone may be of benefit but are often accompanied by intolerable side effects Response to ethanol on the other hand has a roughly 80 chance of significant tremor reduction though daily use of this as a treatment has potentially serious medical social and legal consequences
The leading hypothesis for ET pathophysiology is an unmasking of spontaneous oscillations originating in neurons of the inferior olive Both ethanol and 1-octanol have been shown to reduce these spontaneous oscillations in an animal model of ET however 1-octanol does this at a dose much lower than that leading to intoxication suggesting it may be useful in the treatment of essential tremor Our initial studies with 1-octanol have shown it to be safe at dosages up to 64mgkg without signs of intoxication while at the same time showing benefit
OBJECTIVE
We plan to evaluate the efficacy of different 1-octanol formulations in humans based on accelerometry and spirography We will also evaluate drug and metabolite bioavailabilities using a high performance liquid chromatography HPLC detection method from plasma and urine samples
STUDY POPULATION
We will study adult subjects with ethanol-responsive Essential Tremor ET
DESIGN
This study is designed as a two-phase unblinded inpatient study of adults with ET receiving weight-adjusted oral dosages of 2 different formulations of 1-octanol in a crossover fashion Phase I of the study is designed to develop an octanol detection assay using HPLC Four subjects will receive daily escalating dosages 1-32 mgkg of a single 1-octanol formulation followed by a crossover trial of both formulations at a dosage of 64 mgkg Phase II will study 20 subjects receiving one of the two formulations at 64 mgkg on inpatient day 1 followed by a 24 hour period of close monitoring The second formulation will be given on day 3 and the patient will again undergo close monitoring for 24 hours
OUTCOME MEASURES
The primary outcome measures for the study will be efficacy based on tremor ratings from accelerometry and spirography Secondary outcome measures will be the determination of bioavailability pharmacodynamic and pharmacokinetic profiles of octanol 61864 and octanol 68751 and their metabolites
Addendum Based on the results of the assays for all subjects who participated in Part 1 and 2 of this protocol we would like to conduct an exploratory study Part 3 consisting of two subjects receiving a dose of 128mgkg of 1-octanol This is meant to primarily explore the plasma concentration of 1-octanol while also providing valuable information regarding the safety and efficacy at this higher dose The remainder of the experimental design will be maintained with exception of additional safety precautions which will be discussed in the protocol and consent
Essential tremor ET is a common movement disorder affecting 04 of the general population and up to 14 of people 65 years and older Response to medications such as beta blockers and primidone may be of benefit but are often accompanied by intolerable side effects Response to ethanol on the other hand has a roughly 80 chance of significant tremor reduction though daily use of this as a treatment has potentially serious medical social and legal consequences
The leading hypothesis for ET pathophysiology is an unmasking of spontaneous oscillations originating in neurons of the inferior olive Both ethanol and 1-octanol have been shown to reduce these spontaneous oscillations in an animal model of ET however 1-octanol does this at a dose much lower than that leading to intoxication suggesting it may be useful in the treatment of essential tremor Our initial studies with 1-octanol have shown it to be safe at dosages up to 64mgkg without signs of intoxication while at the same time showing benefit
OBJECTIVE
We plan to evaluate the efficacy of different 1-octanol formulations in humans based on accelerometry and spirography We will also evaluate drug and metabolite bioavailabilities using a high performance liquid chromatography HPLC detection method from plasma and urine samples
STUDY POPULATION
We will study adult subjects with ethanol-responsive Essential Tremor ET
DESIGN
This study is designed as a two-phase unblinded inpatient study of adults with ET receiving weight-adjusted oral dosages of 2 different formulations of 1-octanol in a crossover fashion Phase I of the study is designed to develop an octanol detection assay using HPLC Four subjects will receive daily escalating dosages 1-32 mgkg of a single 1-octanol formulation followed by a crossover trial of both formulations at a dosage of 64 mgkg Phase II will study 20 subjects receiving one of the two formulations at 64 mgkg on inpatient day 1 followed by a 24 hour period of close monitoring The second formulation will be given on day 3 and the patient will again undergo close monitoring for 24 hours
OUTCOME MEASURES
The primary outcome measures for the study will be efficacy based on tremor ratings from accelerometry and spirography Secondary outcome measures will be the determination of bioavailability pharmacodynamic and pharmacokinetic profiles of octanol 61864 and octanol 68751 and their metabolites
Addendum Based on the results of the assays for all subjects who participated in Part 1 and 2 of this protocol we would like to conduct an exploratory study Part 3 consisting of two subjects receiving a dose of 128mgkg of 1-octanol This is meant to primarily explore the plasma concentration of 1-octanol while also providing valuable information regarding the safety and efficacy at this higher dose The remainder of the experimental design will be maintained with exception of additional safety precautions which will be discussed in the protocol and consent
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-N-0092 | None | None | None |