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PK Sampling After IV Oxytocin and Effects on Sensory Function in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT03929367
Recruitment Status : Recruiting
First Posted : April 26, 2019
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:

The primary goal of this protocol is to model change in oxytocin concentrations in plasma after intravenous (IV) administration. Additional measurements will be performed on sensory function that could be influenced by oxytocin during later time periods when blood samples are widely separated by time. This protocol will describe the pharmacokinetics (PK) of intravenous oxytocin in healthy adult men and adult,non-pregnant women. PK samples will be obtained after an injection of intravenous oxytocin 10 IU over 60 seconds.

Blood will be drawn for the PK samples prior to the oxytocin administration and then 11 times after administration.

There are two additional measures which will assess two different aspects of sensory function.

MEASURE 1: Light Touch Frequency Threshold In order to determine the highest frequency that specific nerve fibers can respond to, a simple device that produces an oscillatory / vibratory stimulus will be used on the hand. The subject places fingertips, palm, and palm side of the wrist sequentially and the device is set to slowly decrease the frequency of vibration from 1 kHz until the subject first perceives this. This is repeated three times at each site and takes less than 5 minutes in total. This will be performed before the oxytocin administration and 6 times after the administration of IV Oxytocin.

MEASURE 2: Sustained Heat The surface of the skin of the forearm or leg is heated to 113°F using a computer controlled thermode for a period of 5 minutes. This will be done before the IV Oxytocin and 4 times after the administration. A set of random thermal temperatures (98°F-122°F) will also be applied to the skin of the leg or forearm before the IV Oxytocin administration and 4 times after administration of IV Oxytocin.


Condition or disease Intervention/treatment Phase
Chronic Pain Drug: Oxytocin Phase 4

Detailed Description:

The primary goal of this protocol is to model change in oxytocin concentrations in plasma after intravenous administration, (oxytocin (Pitocin®), 10 IU) the investigators will also acquire tests of sensory function that could be modulated by oxytocin during later time periods when blood samples are widely separated by time. There are two measures which will assess two different aspects of sensory function.

MEASURE 1: Light Touch Frequency Threshold Light touch is subserved by a group of myelinated peripheral nerves with fast conduction in the Aβ range and which are capable of following high frequencies, being responsible for the sensation of vibration. This capability of individual nerve fibers to respond with high frequency also underlies our ability to sense a light touch moving across the body surface as in brushing.

In preclinical studies investigators have shown that, following injury, these light touch fibers lose their ability to follow high frequencies and, in some cases, no longer respond to mechanical stimulation at all. Oxytocin, when perfused around the neuronal cell bodies of these Aβ nerve fibers, partially restores their function, including their response to high frequency stimulation.

In order to determine the highest frequency that Aβ nerve fibers can respond to, the investigators have created a simple device that produces an oscillatory / vibratory stimulus which can be used on the hand. The subject places fingertips, palm, and volar aspect of the wrist sequentially and the device is set to slowly decrease the frequency of vibration from 1 kilohertz (kHz) until the participant first perceives this. This is repeated three times at each site and takes under 5 minutes in total.

The investigators anticipate that oxytocin will have no effect on normal Aβ fibers and that this measure will not change after oxytocin administration. This will provide important data to contrast with the expected efficacy of oxytocin in the setting of injury, to be studied in subsequent protocols.

MEASURE 2: Sustained Heat As part of a protocol used by the investigators in several studies, the surface of the skin of the forearm or leg is heated to 45°C using a computer-controlled thermode for a period of 5 minutes. This typically results in a slowly increasing pain experience, peaking at 5 minutes in the mild to low moderate range and has been tolerated by more than 150 subjects in studies over the past 14 years.

In an interim analysis of an ongoing clinical study in volunteers, the investigators noted that spinal injection of oxytocin, 15 μg (equivalent to 9 IU), that pain from this sustained heat was dramatically reduced over the 5 minutes of stimulus presentation. In contrast, spinal oxytocin had no effect on the stimulus-response relationship of pain to noxious heat over a 42-50°C range when the stimuli were presented for only 5 seconds. These data suggest that oxytocin reduces C-fiber mediated signaling of sustained heat pain, likely through a spinal site of action.

Drugs administered spinally have a much higher concentration in cerebrospinal fluid than plasma. Nonetheless, spinally administered drugs are typically absorbed to an extent and with a time course similar to that after intramuscular injection, and it is conceivable that the effect on sustained heat pain investigators are seeing in the spinal study reflect peripheral effects via systemic absorption. Thus, if the investigators see a similar reduction in response to sustained heat in this protocol of intravenous administration, the investigators will conclude that oxytocin is more likely activating peripherally than spinally.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single intravenous administration of oxytocin (Pitocin®), 10 IU
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pharmacokinetics of Intravenous Oxytocin and Effects on Sensory Function in Healthy Volunteers
Actual Study Start Date : May 10, 2019
Estimated Primary Completion Date : December 15, 2019
Estimated Study Completion Date : December 31, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Oxytocin

Arm Intervention/treatment
Oxytocin (Pitocin®), 10 IU
Oxytocin 10 IU administered once per intravenous injection
Drug: Oxytocin
Single IV administration of oxytocin
Other Name: Pitocin




Primary Outcome Measures :
  1. Oxytocin Concentration [ Time Frame: 2 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  2. Oxytocin Concentration [ Time Frame: 5 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  3. Oxytocin Concentration [ Time Frame: 10 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  4. Oxytocin Concentration [ Time Frame: 15 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  5. Oxytocin Concentration [ Time Frame: 30 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  6. Oxytocin Concentration [ Time Frame: 45 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  7. Oxytocin Concentration [ Time Frame: 60 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  8. Oxytocin Concentration [ Time Frame: 90 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  9. Oxytocin Concentration [ Time Frame: 120 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  10. Oxytocin Concentration [ Time Frame: 180 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion

  11. Oxytocin Concentration [ Time Frame: 240 minutes ]
    Plasma concentrations of oxytocin at defined times after intravenous infusion


Secondary Outcome Measures :
  1. Light Touch Frequency Threshold [ Time Frame: 5 minutes ]
    The frequency at which the vibration is perceived after intravenous oxytocin administration

  2. Light Touch Frequency Threshold [ Time Frame: 20 minutes ]
    The frequency at which the vibration is perceived after intravenous oxytocin administration

  3. Light Touch Frequency Threshold [ Time Frame: 45 minutes ]
    The frequency at which the vibration is perceived after intravenous oxytocin administration

  4. Light Touch Frequency Threshold [ Time Frame: 60 minutes ]
    The frequency at which the vibration is perceived after intravenous oxytocin administration

  5. Light Touch Frequency Threshold [ Time Frame: 120 minutes ]
    The frequency at which the vibration is perceived after intravenous oxytocin administration

  6. Light Touch Frequency Threshold [ Time Frame: 180 minutes ]
    The frequency at which the vibration is perceived after intravenous oxytocin administration

  7. Sustained Heat [ Time Frame: 31 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  8. Sustained Heat [ Time Frame: 32 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  9. Sustained Heat [ Time Frame: 33 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  10. Sustained Heat [ Time Frame: 34 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  11. Sustained Heat [ Time Frame: 35 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  12. Sustained Heat [ Time Frame: 61 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  13. Sustained Heat [ Time Frame: 62 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  14. Sustained Heat [ Time Frame: 63 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  15. Sustained Heat [ Time Frame: 64 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  16. Sustained Heat [ Time Frame: 65 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  17. Sustained Heat [ Time Frame: 121 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  18. Sustained Heat [ Time Frame: 122 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  19. Sustained Heat [ Time Frame: 123 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  20. Sustained Heat [ Time Frame: 124 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  21. Sustained Heat [ Time Frame: 125 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  22. Sustained Heat [ Time Frame: 181 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  23. Sustained Heat [ Time Frame: 182 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  24. Sustained Heat [ Time Frame: 183 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  25. Sustained Heat [ Time Frame: 184 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.

  26. Sustained Heat [ Time Frame: 185 minutes ]
    0-10 verbal pain score to a 45 degree Celsius stimulus after intravenous oxytocin administration; higher score denotes worse outcome.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female > 18 and < 60 years of age, Body Mass Index (BMI) <40.
  • Generally in good health as determined by the Principal Investigator based on prior medical history, American Society of Anesthesiologists physical status I or II
  • Normal blood pressure (systolic 90-140 mmHg; diastolic 50-90 mmHg) resting heart rate 45-100 beats per minute) without medication
  • Female subjects of child-bearing potential and those < 1 year post-menopausal, must be practicing highly effective methods of birth control such as hormonal methods

Exclusion Criteria:

  • Hypersensitivity, allergy, or significant reaction to any ingredient of Pitocin®
  • Any disease, diagnosis, or condition (medical or surgical) that, in the opinion of the Principal Investigator, would place the subject at increased risk (active gynecologic disease in which increased tone would be detrimental e.g., uterine fibroids with ongoing bleeding), compromise the subject's compliance with study procedures, or compromise the quality of the data
  • Women who are pregnant (positive result for serum pregnancy test at screening visit), women who are currently nursing or lactating, women that have been pregnant within 2 years
  • Subjects with neuropathy, chronic pain, diabetes mellitus, or taking benzodiazepines or pain medications on a daily basis.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03929367


Contacts
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Contact: Regina Curry, RN 336-716-4294 RECURRY@WAKEHEALTH.EDU

Locations
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United States, North Carolina
Wake Forest Baptist Medical Center Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Regina Curry, RN    336-716-4294    recurry@wakehealth.edu   
Principal Investigator: James C Eisenach, MD         
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
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Principal Investigator: James Eisenach, MD Wake Forest University Health Sciences

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03929367     History of Changes
Other Study ID Numbers: IRB00056413
First Posted: April 26, 2019    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: Yes

Additional relevant MeSH terms:
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Chronic Pain
Pain
Neurologic Manifestations
Signs and Symptoms
Oxytocin
Oxytocics
Reproductive Control Agents
Physiological Effects of Drugs