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

Pilot Study to Assess the Safety, Tolerability, and Feasibility of Administering Clonidine as a Pharmacological Challenge in Future Imaging Studies of Cerebrospinal Fluid Kinetics

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.

Study Overview

• Status: Terminated
• Conditions: Cancer; Neuro-Degenerative Disease
• Intervention / Treatment: Drug: Clonidine Pill

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: Interventional
• Enrollment (Actual): 3
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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 Names: On-Drug

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Total Sleep Duration	Time interval between falling asleep and waking up as estimated by a wearable sleep tracking device	Day 2 and Day 8 on drug and Day 16 washout compared to Day (-7) through Day 1 during drug-free lead-in
Change in Deep Sleep Time	amount of time estimated to be in deep sleep versus light sleep by a wearable sleep tracking device	Day 2 and Day 8 on drug and Day 16 washout compared to Day (-7) through Day 1 during drug-free lead-in

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: P. David Mozley, MD, Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2019
• Primary Completion (Actual): March 17, 2020
• Study Completion (Actual): March 17, 2020

Study Registration Dates

• First Submitted: July 22, 2019
• First Submitted That Met QC Criteria: July 23, 2019
• First Posted (Actual): July 24, 2019

Study Record Updates

• Last Update Posted (Actual): June 24, 2021
• Last Update Submitted That Met QC Criteria: June 21, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurodegenerative Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Sympatholytics; Clonidine
• Other Study ID Numbers: 19-04020242

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All de-identified on-study data will be shared.
• IPD Sharing Time Frame: Data will be made available within six months of last study visit or acceptance for publication, whichever comes first.
• IPD Sharing Access Criteria: Any reasonable request sent to dvm9029@med.cornell.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; CSR

Drug and device information, study documents

• 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