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Hydromorphone Pharmacokinetic-Pharmacodynamic Fingerprint

This study is enrolling participants by invitation only.
Sponsor:
Information provided by (Responsible Party):
Dhanesh Gupta, Northwestern University
ClinicalTrials.gov Identifier:
NCT01123486
First received: May 10, 2010
Last updated: January 28, 2014
Last verified: January 2014
  Purpose

The primary objective of the proposed work is development of a high resolution pharmacokinetic-pharmacodynamic (PK-PD) model of hydromorphone for experimental pain stimuli, ventilatory depression, and surrogate biomarkers of opioid effect that will allow the fingerprinting of hydromorphone. This fingerprint will serve as the basis for the development of dosing strategies that efficiently maximize analgesia while minimizing ventilatory depression and sedation. For example, this high-resolution fingerprint will allow precise estimation of an initial hydromorphone target effect site concentration (Ce) from those of effectively administered synthetic opioids with previously determined high-resolution fingerprints (i.e., remifentanil or fentanyl), thereby minimizing underdosing of hydromorphone for analgesia and minimizing side effects.


Condition Intervention
Pain
Ventilatory Depression
Drug: hydromorphone

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Hydromorphone High Resolution Pharmacokinetic-Pharmacodynamic Fingerprint as the Basis for Identifying Sex Differences in Opioid Pharmacokinetics and Pharmacodynamics

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Opioid induced analgesia [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    A combined PK-PD model for hydromorphone induced analgesia (heat pain tolerance) will be developed

  • Opioid induced miosis [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    A combined PK-PD model for hydromorphone induced miosis will be developed

  • Opioid induced EEG changes [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    A combined PK-PD model for hydromorphone induced EEG effects will be developed


Secondary Outcome Measures:
  • Opioid induced ventilatory depression [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]
    A combined PK-PD model for hydromorphone induced ventilatory depression will be created


Estimated Enrollment: 24
Study Start Date: January 2015
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: hydromorphone
open label single arm pharmacokinetic-pharmacodynamic study
Drug: hydromorphone
hydromorphone 0.02 mg/kg
Other Name: Dilaudid

Detailed Description:

After 6 h of fasting, each volunteer will have a 20G arterial-line placed in the radial artery for early blood sampling and an 18 G peripheral intravenous catheter placed in the contralateral forearm for drug administration and later blood sampling. Continuously monitored vital signs will include ECG, invasive blood pressure, hemoglobin, O2 saturation, end-tidal CO2, and respiratory rate (from the capnogram) recorded.

After baseline PD data acquisition, a bolus of 0.2 mg/kg hydromorphone will be administered over 10 sec via the free-flowing peripheral IV (t=0) and 3 mL arterial blood samples will be obtained at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, and 2 min using a stop-cock and manifold system. Subsequent blood samples will be acquired at 3, 4, 5, 7.5, 10, 15, 20, 25, 30, and 45 min and 1, 1.25, 1.5, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 6, 7, 8, 10, 12, 16, 20, and 24 h. Although EEG will be acquired continuously, the remaining pharmacologic data will be recorded at discrete times s in the initial 5 min: pupillometry at 1, 2, and 5 min; ventilation at 2 min; temperature analgesia at 3 and 5 min, and sedation level at 4 min. This will allow the ventilation and pupillometry to be acquired in a resting state, thereby limiting distortion of these responses by stimulation. Subsequently, all data will be acquired at all PK time points in the following sequence - ventilation and EEG (simultaneously), pupillometry, modified OAA/S score, and temperature analgesia. After 2 h, once a pharmacologic parameter has returned to baseline for 2 sequential measurements, recording of that parameter will be stopped. During the study, if the volunteer is unable to use the device trigger, due to opioid-induced sedation, the tolerance level for increased temperature will be defined as the temperature at which the volunteer exhibits withdrawal movement of the tested limb. Once all data acquisition has been completed, the volunteer will be allowed to drink clear liquids. Subsequently, the diet will be advanced as tolerated. The volunteer will be monitored hourly (vital signs) in the Clinical Research Unit until all of the blood samples have been acquired.

  Eligibility

Ages Eligible for Study:   21 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • within 20% of their ideal body weight
  • 21-30 years old
  • ASA I (no systemic disease)
  • No history of PONV (except wisdom teeth extraction)
  • No long term medication use
  • No history of coagulation defect (i.e easy bruising, gum bleeding with teeth brushing, frequent nose bleeds, past documented coagulopathy, etc.)

Exclusion Criteria:

  • Inability to place an arterial line
  • A failed urine drug test on admission to the CRU
  • A positive pregnancy test on admission to the CRU
  • A hemoglobin level < 12.5 g/dL on admission to the CRU
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01123486

Locations
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Dhanesh K. Gupta, M.D. Departments of Anesthesiology & Neurological Surgery, Northwestern University Feinberg School of Medicine
  More Information

Publications:

Responsible Party: Dhanesh Gupta, Associate Professor of Anesthesiology & Neurological Surgery, Northwestern University
ClinicalTrials.gov Identifier: NCT01123486     History of Changes
Other Study ID Numbers: STU00013543
Study First Received: May 10, 2010
Last Updated: January 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Northwestern University:
Intravenous opioids
Patient Controlled Analgesia
volunteer pharmacokinetic-pharmacodynamic study

Additional relevant MeSH terms:
Depression
Respiratory Insufficiency
Behavioral Symptoms
Respiration Disorders
Respiratory Tract Diseases
Hydromorphone
Analgesics
Analgesics, Opioid
Central Nervous System Agents
Central Nervous System Depressants
Narcotics
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014