PainNCT01123486
Hydromorphone Pharmacokinetic-Pharmacodynamic Fingerprint
A study testing hydromorphone in people with Pain and Ventilatory Depression, run by Northwestern University at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Pain, Ventilatory Depression
- What is being tested?
- hydromorphone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2015to Jan 2015
- Phase
- Interventional
- 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 21 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Northwestern Memorial Hospital
Chicago, Illinois, 60611
About this study
Official title: A Hydromorphone High Resolution Pharmacokinetic-Pharmacodynamic Fingerprint as the Basis for Identifying Sex Differences in Opioid Pharmacokinetics and Pharmacodynamics
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.
Read the 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.
- Conditions
- Pain, Ventilatory Depression
- Being tested
- hydromorphone
- Keywords
- Intravenous opioids, Patient Controlled Analgesia, volunteer pharmacokinetic-pharmacodynamic study
- Medical subject headings
- Pain, Respiratory Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hydromorphoneDrug
Also called Dilaudid
hydromorphone 0.02 mg/kg
| Study group | Role | What they receive |
|---|---|---|
| hydromorphone | Experimental | open label single arm pharmacokinetic-pharmacodynamic study Receives: Drug: hydromorphone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Opioid induced analgesia
A combined PK-PD model for hydromorphone induced analgesia (heat pain tolerance) will be developed
Measured: 24 hours
Secondary outcomes (3)
Opioid induced ventilatory depression
A combined PK-PD model for hydromorphone induced ventilatory depression will be created
Measured: 24 hours
Opioid induced miosis
A combined PK-PD model for hydromorphone induced miosis will be developed
Measured: 24 hours
Opioid induced EEG changes
A combined PK-PD model for hydromorphone induced EEG effects will be developed
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2010 (estimated)
- Study startJan 2015
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: PI relocated to new university
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (46)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- More trials run by Northwestern UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Northwestern University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dhanesh Gupta, Northwestern University
- Investigators
- Dhanesh K. Gupta, M.D., Principal investigator, Departments of Anesthesiology & Neurological Surgery, Northwestern University Feinberg School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01123486
- Sponsor's protocol ID
- STU00013543
- Status last verified
- Apr 2015
- First submitted
- 10 May 2010
- Last updated
- 22 Apr 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Upton RN, Semple TJ, Macintyre PE. Pharmacokinetic optimisation of opioid treatment in acute pain therapy. Clin Pharmacokinet. 1997 Sep;33(3):225-44. doi: 10.2165/00003088-199733030-00005.
PubMed 9314613Stanski DR, Hug CC Jr. Alfentanil--a kinetically predictable narcotic analgesic. Anesthesiology. 1982 Dec;57(6):435-8. doi: 10.1097/00000542-198212000-00001. No abstract available.
PubMed 6128947Scott JC, Ponganis KV, Stanski DR. EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil. Anesthesiology. 1985 Mar;62(3):234-41. doi: 10.1097/00000542-198503000-00005.
PubMed 3919613Maitre PO, Vozeh S, Heykants J, Thomson DA, Stanski DR. Population pharmacokinetics of alfentanil: the average dose-plasma concentration relationship and interindividual variability in patients. Anesthesiology. 1987 Jan;66(1):3-12.
PubMed 3099604Scott JC, Stanski DR. Decreased fentanyl and alfentanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther. 1987 Jan;240(1):159-66.
PubMed 3100765Scott JC, Cooke JE, Stanski DR. Electroencephalographic quantitation of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil. Anesthesiology. 1991 Jan;74(1):34-42. doi: 10.1097/00000542-199101000-00007.
PubMed 1670913Bjorkman S, Wada DR, Stanski DR, Ebling WF. Comparative physiological pharmacokinetics of fentanyl and alfentanil in rats and humans based on parametric single-tissue models. J Pharmacokinet Biopharm. 1994 Oct;22(5):381-410. doi: 10.1007/BF02353862.
PubMed 7791038Egan TD, Minto CF, Hermann DJ, Barr J, Muir KT, Shafer SL. Remifentanil versus alfentanil: comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers. Anesthesiology. 1996 Apr;84(4):821-33. doi: 10.1097/00000542-199604000-00009.
PubMed 8638836Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, Billard V, Hoke JF, Moore KH, Hermann DJ, Muir KT, Mandema JW, Shafer SL. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology. 1997 Jan;86(1):10-23. doi: 10.1097/00000542-199701000-00004.
PubMed 9009935Minto CF, Schnider TW, Shafer SL. Pharmacokinetics and pharmacodynamics of remifentanil. II. Model application. Anesthesiology. 1997 Jan;86(1):24-33. doi: 10.1097/00000542-199701000-00005.
PubMed 9009936Egan TD, Lemmens HJ, Fiset P, Hermann DJ, Muir KT, Stanski DR, Shafer SL. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology. 1993 Nov;79(5):881-92. doi: 10.1097/00000542-199311000-00004.
PubMed 7902032Segre G. Kinetics of interaction between drugs and biological systems. Farmaco Sci. 1968 Oct;23(10):907-18. No abstract available.
PubMed 5712792Sheiner LB, Stanski DR, Vozeh S, Miller RD, Ham J. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther. 1979 Mar;25(3):358-71. doi: 10.1002/cpt1979253358.
PubMed 761446Ebling WF, Lee EN, Stanski DR. Understanding pharmacokinetics and pharmacodynamics through computer stimulation: I. The comparative clinical profiles of fentanyl and alfentanil. Anesthesiology. 1990 Apr;72(4):650-8. doi: 10.1097/00000542-199004000-00013.
PubMed 2321782Gregg KM, Varvel JR, Shafer SL. Application of semilinear canonical correlation to the measurement of opioid drug effect. J Pharmacokinet Biopharm. 1992 Dec;20(6):611-35. doi: 10.1007/BF01064422.
PubMed 1302765
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Hydromorphone High Resolution Pharmacokinetic-Pharmacodynamic Fingerprint as the Basis for Identifying Sex Differences in Opioid Pharmacokinetics and Pharmacodynamics
- ClinicalTrials.gov ID
- NCT01123486
- Acronym / sponsor ID
- STU00013543
- Conditions
- Pain, Ventilatory Depression
- Keywords
- Intravenous opioids, Patient Controlled Analgesia, volunteer pharmacokinetic-pharmacodynamic study
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI relocated to new university
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Northwestern UniversityUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 14 May 2010 (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.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| hydromorphone | Experimental | Drug: hydromorphoneopen label single arm pharmacokinetic-pharmacodynamic study |
Who may qualify
- Ages
- 21 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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
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 |
|---|---|---|
| hydromorphoneAlso: Dilaudidhydromorphone 0.02 mg/kg | Drug | hydromorphone |
Primary outcome
Opioid induced analgesia
Time frame: 24 hours
A combined PK-PD model for hydromorphone induced analgesia (heat pain tolerance) will be developed
3 secondary outcomes
Opioid induced ventilatory depression
Time frame: 24 hours
Opioid induced miosis
Time frame: 24 hours
Opioid induced EEG changes
Time frame: 24 hours
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2015.
- Background: PubMed 9314613Upton RN, Semple TJ, Macintyre PE. Pharmacokinetic optimisation of opioid treatment in acute pain therapy. Clin Pharmacokinet. 1997 Sep;33(3):225-44. doi: 10.2165/00003088-199733030-00005.
- Background: PubMed 6128947Stanski DR, Hug CC Jr. Alfentanil--a kinetically predictable narcotic analgesic. Anesthesiology. 1982 Dec;57(6):435-8. doi: 10.1097/00000542-198212000-00001. No abstract available.
- Background: PubMed 3919613Scott JC, Ponganis KV, Stanski DR. EEG quantitation of narcotic effect: the comparative pharmacodynamics of fentanyl and alfentanil. Anesthesiology. 1985 Mar;62(3):234-41. doi: 10.1097/00000542-198503000-00005.
- Background: PubMed 3099604Maitre PO, Vozeh S, Heykants J, Thomson DA, Stanski DR. Population pharmacokinetics of alfentanil: the average dose-plasma concentration relationship and interindividual variability in patients. Anesthesiology. 1987 Jan;66(1):3-12.
- Background: PubMed 3100765Scott JC, Stanski DR. Decreased fentanyl and alfentanil dose requirements with age. A simultaneous pharmacokinetic and pharmacodynamic evaluation. J Pharmacol Exp Ther. 1987 Jan;240(1):159-66.
- Background: PubMed 1670913Scott JC, Cooke JE, Stanski DR. Electroencephalographic quantitation of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil. Anesthesiology. 1991 Jan;74(1):34-42. doi: 10.1097/00000542-199101000-00007.
- Background: PubMed 7791038Bjorkman S, Wada DR, Stanski DR, Ebling WF. Comparative physiological pharmacokinetics of fentanyl and alfentanil in rats and humans based on parametric single-tissue models. J Pharmacokinet Biopharm. 1994 Oct;22(5):381-410. doi: 10.1007/BF02353862.
- Background: PubMed 8638836Egan TD, Minto CF, Hermann DJ, Barr J, Muir KT, Shafer SL. Remifentanil versus alfentanil: comparative pharmacokinetics and pharmacodynamics in healthy adult male volunteers. Anesthesiology. 1996 Apr;84(4):821-33. doi: 10.1097/00000542-199604000-00009.
- Background: PubMed 9009935Minto CF, Schnider TW, Egan TD, Youngs E, Lemmens HJ, Gambus PL, Billard V, Hoke JF, Moore KH, Hermann DJ, Muir KT, Mandema JW, Shafer SL. Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development. Anesthesiology. 1997 Jan;86(1):10-23. doi: 10.1097/00000542-199701000-00004.
- Background: PubMed 9009936Minto CF, Schnider TW, Shafer SL. Pharmacokinetics and pharmacodynamics of remifentanil. II. Model application. Anesthesiology. 1997 Jan;86(1):24-33. doi: 10.1097/00000542-199701000-00005.
- Background: PubMed 7902032Egan TD, Lemmens HJ, Fiset P, Hermann DJ, Muir KT, Stanski DR, Shafer SL. The pharmacokinetics of the new short-acting opioid remifentanil (GI87084B) in healthy adult male volunteers. Anesthesiology. 1993 Nov;79(5):881-92. doi: 10.1097/00000542-199311000-00004.
- Background: PubMed 5712792Segre G. Kinetics of interaction between drugs and biological systems. Farmaco Sci. 1968 Oct;23(10):907-18. No abstract available.
Related trials for Pain
Not yet recruiting
Effect of Stress Ball Use During Femoral Arterial Sheath Removal After Coronary Angiography
Femoral Arterial Sheath Removal, Stress Ball
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingPhase 4
ESP Blocks for Posterior Spinal Fusion
Postoperative Pain
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effects of Hip Hinge Exercises on Pain, Range of Motion and Functional Disability in Non-specific Low Back Pain.
Low Back Pain
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.
Dhanesh K. Gupta, M.D. principal investigator
Departments of Anesthesiology & Neurological Surgery, Northwestern University Feinberg 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 study testing hydromorphone in people with Pain and Ventilatory Depression, run by Northwestern University 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 6 inclusion and 4 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: withdrawn, as of the sponsor's last update on 22 Apr 2015. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Opioid induced analgesia (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01123486, which also lists 46 linked publications.
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 22 Apr 2015.