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出境医 / 临床实验 / Feasibility of Administering Clonidine as a Pharmacological Challenge in Imaging Studies (a2a Agonist)

Feasibility of Administering Clonidine as a Pharmacological Challenge in Imaging Studies (a2a Agonist)

Study Description
Brief Summary:
This will be a Phase 1, open label study of the pharmacokinetics (PK) and pharmacodynamics (PD) of clonidine, an alpha-2 adrenergic (a2a) agonist, in healthy volunteers. The primary aim is to show that the drug regimen is safe and reasonably well tolerated. The secondary aim is to demonstrate that safety can be monitored with home health devices.

Condition or disease Intervention/treatment Phase
Neuro-Degenerative Disease Cancer Drug: Clonidine Pill Early Phase 1

Detailed Description:

Subjects who screen in will participate in a drug-free lead-in period of one week duration. Then, the drug test article, clonidine HCl, 0.1 mg tabs, will be administered once daily by mouth at bedtime for one week. Steady-state PK will be measured on Day 8 post-drug with a single blood draw of 10 mL. This will be followed by a one week wash out period. During each of these three different one-week periods, sleep quality will be monitored nightly with a blue tooth and wireless enabled, wearable sleep tracker. Vital signs (VSs) will be monitored daily at home with a blue tooth and wireless enabled blood pressure machine. VSs and electrocardiograms (ECGs) will be measured before drug on Day (-7) and Day 1. Repeat measurements will be made during clinic visits on Day 2, Day 8, and Day 16.

The findings should show that there is, or is not, a PD effect produced by this rather low dose of drug administered for a relatively short period of time. Showing a PD effect at a safe and reasonably well tolerated dose would qualify this drug dosing regimen as a pharmacological challenge in future studies.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pilot Study to Assess the Safety, Tolerability, and Feasibility of Administering Clonidine as a Pharmacological Challenge in Future Imaging Studies of Cerebrospinal Fluid Kinetics
Actual Study Start Date : December 10, 2019
Estimated Primary Completion Date : June 30, 2021
Estimated Study Completion Date : December 31, 2021
Arms and Interventions
Arm Intervention/treatment
Experimental: Clonidine Pill
One week period of clonidine, 0.1 mg tabs, one by mouth daily at bedtime
Drug: Clonidine Pill
0.1 mg tabs, one by mouth daily at bedtime for one week
Other Name: On-Drug

Outcome Measures
Primary Outcome Measures :
  1. Number of subjects experiencing adverse events related to drug-induced changes in hemodynamic function. [ Time Frame: Day 2 or Day 8 compared to Day (-7) through Day 1 during drug-free lead-in ]
    clinically significant drop in blood pressure or pulse


Secondary Outcome Measures :
  1. Change in Total Sleep Duration [ Time Frame: Day 2 and Day 8 on drug and Day 16 washout compared to Day (-7) through Day 1 during drug-free lead-in ]
    Time interval between falling asleep and waking up as estimated by a wearable sleep tracking device

  2. Change in Deep Sleep Time [ Time Frame: Day 2 and Day 8 on drug and Day 16 washout compared to Day (-7) through Day 1 during drug-free lead-in ]
    amount of time estimated to be in deep sleep versus light sleep by a wearable sleep tracking device


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • able to give informed consent.
  • age 18-89
  • Subjectively healthy and, in the opinion of the investigators, likely to be compliant with the drug regimen and the schedule of follow up visits.
  • Normal hemodynamic function. Systolic blood pressure and pulse must be higher than 120 mmHg and 60 beats per minute while sitting. At the discretion of the investigators, athletic people who are in exceptionally robust condition may be enrolled if their systolic blood pressure and pulse are higher than 100 mmHg and 50 beats per minute while sitting.
  • Unremarkable electrocardiograms with PR intervals of less than 200 mSec and QT intervals corrected with Fridericia's method (QTcF) of less than 440 mSec.
  • No concurrent medications with the exception of p.r.n. NSAIDS, which must be discontinued one week prior to the lead-in period, and avoided for the next three weeks while on study (the one week lead-in period, one week on drug period, and one week washout period).
  • Willing and able to refrain from abusing any recreational drugs, including marijuana because of its sleep effects, and drink less than one unit of alcoholic beverages per day starting one week prior to the lead-in period, and avoided for the next three weeks while on study (the one week lead-in period, one week on drug period, and one week washout period).
  • Willing to refrain from donating blood while during the month of study.
  • Willing to refrain from participating in any other research study that requires taking medication during the month of study.
  • Willing to refrain from being vaccinated during the month of study.

Exclusion Criteria:

  • History of allergy to clonidine.
  • History of multiple hypersensitivity reactions, as indicated by allergies to multiple medications, foods, and seasonal pollen.
  • History or physical examination suggestive of a condition, disorder, or disease that could represent a contra-indication to taking an antihypertensive. The relative contraindications to clonidine listed in the package insert under the section on precautions will be exclusionary in this study. They include subjects with coronary artery insufficiency syndromes, histories of myocardial infarction, cardiac conduction abnormalities, cerebrovascular disease, and chronic renal failure.
  • Women who are pregnant or breast feeding will not be eligible to participate in the study, as clonidine is classified as a Class C risk to a fetus. (In fact, there is a safety signal in pregnant animal models that justifies exclusion, even if the signal is weak.)
  • History or physical examination suggestive of a condition, disorder, or disease that could affect the adsorption, distribution, metabolism or excretion of the study drug.
  • Positive urine toxicology screen for recreational drugs, other than cannabis.
  • History of attention deficit hyperactivity disorder (ADHD) as a child or a residual disorder as an adult, because safety, tolerability, and patient acceptability have already been shown in these populations.
  • Subjects may not be a member of a vulnerable population.
  • May not have taken any controlled medications, including other study drugs, in the last 30 days or for 10 half-lives, whichever is longer.
  • May not have donated blood in the 30 days prior to the start of the lead-in period.
  • May not have participated in research administering drugs in the last 30 days.
  • May not have been vaccinated in the 30 days prior to the start of the lead-in period.
Contacts and Locations

Contacts
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Contact: P. David Mozley, MD 212 746 5805 dvm9029@med.cornell.edu
Contact: Weill Medical College of Cornell University 646 962 8200 jcto@med.cornell.edu

Locations
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United States, New York
Weill Cornell Medicine Recruiting
New York, New York, United States, 10065
Contact: P. David Mozley, MD    212-746-5805    dvm9029@med.cornell.edu   
Sponsors and Collaborators
Weill Medical College of Cornell University
Investigators
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Principal Investigator: P. David Mozley, MD Weill Medical College of Cornell University
Tracking Information
First Submitted Date  ICMJE July 22, 2019
First Posted Date  ICMJE July 24, 2019
Last Update Posted Date August 25, 2020
Actual Study Start Date  ICMJE December 10, 2019
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
Number of subjects experiencing adverse events related to drug-induced changes in hemodynamic function. [ Time Frame: Day 2 or Day 8 compared to Day (-7) through Day 1 during drug-free lead-in ]
clinically significant drop in blood pressure or pulse
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 23, 2019)
  • Change in Total Sleep Duration [ Time Frame: Day 2 and Day 8 on drug and Day 16 washout compared to Day (-7) through Day 1 during drug-free lead-in ]
    Time interval between falling asleep and waking up as estimated by a wearable sleep tracking device
  • Change in Deep Sleep Time [ Time Frame: Day 2 and Day 8 on drug and Day 16 washout compared to Day (-7) through Day 1 during drug-free lead-in ]
    amount of time estimated to be in deep sleep versus light sleep by a wearable sleep tracking device
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Feasibility of Administering Clonidine as a Pharmacological Challenge in Imaging Studies
Official Title  ICMJE Pilot Study to Assess the Safety, Tolerability, and Feasibility of Administering Clonidine as a Pharmacological Challenge in Future Imaging Studies of Cerebrospinal Fluid Kinetics
Brief Summary This will be a Phase 1, open label study of the pharmacokinetics (PK) and pharmacodynamics (PD) of clonidine, an alpha-2 adrenergic (a2a) agonist, in healthy volunteers. The primary aim is to show that the drug regimen is safe and reasonably well tolerated. The secondary aim is to demonstrate that safety can be monitored with home health devices.
Detailed Description

Subjects who screen in will participate in a drug-free lead-in period of one week duration. Then, the drug test article, clonidine HCl, 0.1 mg tabs, will be administered once daily by mouth at bedtime for one week. Steady-state PK will be measured on Day 8 post-drug with a single blood draw of 10 mL. This will be followed by a one week wash out period. During each of these three different one-week periods, sleep quality will be monitored nightly with a blue tooth and wireless enabled, wearable sleep tracker. Vital signs (VSs) will be monitored daily at home with a blue tooth and wireless enabled blood pressure machine. VSs and electrocardiograms (ECGs) will be measured before drug on Day (-7) and Day 1. Repeat measurements will be made during clinic visits on Day 2, Day 8, and Day 16.

The findings should show that there is, or is not, a PD effect produced by this rather low dose of drug administered for a relatively short period of time. Showing a PD effect at a safe and reasonably well tolerated dose would qualify this drug dosing regimen as a pharmacological challenge in future studies.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Neuro-Degenerative Disease
  • Cancer
Intervention  ICMJE Drug: Clonidine Pill
0.1 mg tabs, one by mouth daily at bedtime for one week
Other Name: On-Drug
Study Arms  ICMJE Experimental: Clonidine Pill
One week period of clonidine, 0.1 mg tabs, one by mouth daily at bedtime
Intervention: Drug: Clonidine Pill
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 23, 2019)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date June 30, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • able to give informed consent.
  • age 18-89
  • Subjectively healthy and, in the opinion of the investigators, likely to be compliant with the drug regimen and the schedule of follow up visits.
  • Normal hemodynamic function. Systolic blood pressure and pulse must be higher than 120 mmHg and 60 beats per minute while sitting. At the discretion of the investigators, athletic people who are in exceptionally robust condition may be enrolled if their systolic blood pressure and pulse are higher than 100 mmHg and 50 beats per minute while sitting.
  • Unremarkable electrocardiograms with PR intervals of less than 200 mSec and QT intervals corrected with Fridericia's method (QTcF) of less than 440 mSec.
  • No concurrent medications with the exception of p.r.n. NSAIDS, which must be discontinued one week prior to the lead-in period, and avoided for the next three weeks while on study (the one week lead-in period, one week on drug period, and one week washout period).
  • Willing and able to refrain from abusing any recreational drugs, including marijuana because of its sleep effects, and drink less than one unit of alcoholic beverages per day starting one week prior to the lead-in period, and avoided for the next three weeks while on study (the one week lead-in period, one week on drug period, and one week washout period).
  • Willing to refrain from donating blood while during the month of study.
  • Willing to refrain from participating in any other research study that requires taking medication during the month of study.
  • Willing to refrain from being vaccinated during the month of study.

Exclusion Criteria:

  • History of allergy to clonidine.
  • History of multiple hypersensitivity reactions, as indicated by allergies to multiple medications, foods, and seasonal pollen.
  • History or physical examination suggestive of a condition, disorder, or disease that could represent a contra-indication to taking an antihypertensive. The relative contraindications to clonidine listed in the package insert under the section on precautions will be exclusionary in this study. They include subjects with coronary artery insufficiency syndromes, histories of myocardial infarction, cardiac conduction abnormalities, cerebrovascular disease, and chronic renal failure.
  • Women who are pregnant or breast feeding will not be eligible to participate in the study, as clonidine is classified as a Class C risk to a fetus. (In fact, there is a safety signal in pregnant animal models that justifies exclusion, even if the signal is weak.)
  • History or physical examination suggestive of a condition, disorder, or disease that could affect the adsorption, distribution, metabolism or excretion of the study drug.
  • Positive urine toxicology screen for recreational drugs, other than cannabis.
  • History of attention deficit hyperactivity disorder (ADHD) as a child or a residual disorder as an adult, because safety, tolerability, and patient acceptability have already been shown in these populations.
  • Subjects may not be a member of a vulnerable population.
  • May not have taken any controlled medications, including other study drugs, in the last 30 days or for 10 half-lives, whichever is longer.
  • May not have donated blood in the 30 days prior to the start of the lead-in period.
  • May not have participated in research administering drugs in the last 30 days.
  • May not have been vaccinated in the 30 days prior to the start of the lead-in period.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 89 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: P. David Mozley, MD 212 746 5805 dvm9029@med.cornell.edu
Contact: Weill Medical College of Cornell University 646 962 8200 jcto@med.cornell.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04030572
Other Study ID Numbers  ICMJE 19-04020242
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: All de-identified on-study data will be shared.
Supporting Materials: Study Protocol
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data will be made available within six months of last study visit or acceptance for publication, whichever comes first.
Access Criteria: Any reasonable request sent to dvm9029@med.cornell.edu
Responsible Party Weill Medical College of Cornell University
Study Sponsor  ICMJE Weill Medical College of Cornell University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: P. David Mozley, MD Weill Medical College of Cornell University
PRS Account Weill Medical College of Cornell University
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP