Trial record 16 of 169 for:    Open Studies | "Analgesics"

Analgesic Effect of Oxytocin Receptor Modulation

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University Hospital Inselspital, Berne
Sponsor:
Information provided by (Responsible Party):
University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier:
NCT01918475
First received: August 6, 2013
Last updated: February 11, 2014
Last verified: February 2014
  Purpose

Carbetocin is a synthetic analogue of the hormone Oxytocin and is routinely used in obstetric anesthesiology to control uterine bleeding after cesarean section. As an incidental finding, women who received carbetocin had less pain after cesarean section than women who had received Oxytocin. Carbetocin may therefore have an analgesic effect.

The present study examines this analgesic effect using different sensory tests, e.g. pressure, heat, cold and electrical pain before and after administration of carbetocin in healthy male volunteers. Any changes in these sensory tests might be indicative of an analgesic property of carbetocin.


Condition Intervention
Pain
Hyperalgesia
Central Sensitization
Drug: Carbetocin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Analgesic Effect of Oxytocin Receptor Modulation in Healthy Volunteers

Resource links provided by NLM:


Further study details as provided by University Hospital Inselspital, Berne:

Primary Outcome Measures:
  • Change in intramuscular electrical pain threshold compared to baseline [ Time Frame: 10, 60 and 120 minutes after carbeoticin administration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Capsaicin-induced area of hyperalgesia and allodynia [ Time Frame: 10, 60 and 120 minutes after carbeoticin administration ] [ Designated as safety issue: No ]
  • Nociceptive withdrawal reflex thresholds of the foot [ Time Frame: 10, 60 and 120 minutes after carbeoticin administration ] [ Designated as safety issue: No ]
  • Single cutaneous electrical pain thresholds [ Time Frame: 10, 60 and 120 minutes after carbeoticin administration ] [ Designated as safety issue: No ]
  • Repeated cutaneous electrical pain thresholds [ Time Frame: 10, 60 and 120 minutes after carbeoticin administration ] [ Designated as safety issue: No ]
  • Single intramuscular electrical pain threshold [ Time Frame: 10, 60 and 120 minutes after carbeoticin administration ] [ Designated as safety issue: No ]
  • Heat pain detection threshold [ Time Frame: 10, 60 and 120 minutes after carbeoticin administration ] [ Designated as safety issue: No ]
  • Heat pain tolerance threshold [ Time Frame: 10, 60 and 120 minutes after carbetocin administration ] [ Designated as safety issue: No ]

Estimated Enrollment: 25
Study Start Date: July 2013
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Carbetocin first
Subjects receive carbetocin 0.1 mg intravenously in the first session and placebo (NaCl 0.9%) in the second session
Drug: Carbetocin
Carbetocin 0.1 mg single dose is intravenously administered
Drug: Placebo
1ml of NaCl 0.9% is administered intravenously
Active Comparator: Placebo first
Subjects receive placebo (NaCl 0.9%) intravenously in the first session and carbetocin 0.1 mg in the second session
Drug: Carbetocin
Carbetocin 0.1 mg single dose is intravenously administered
Drug: Placebo
1ml of NaCl 0.9% is administered intravenously

Detailed Description:

Background

Chronic pain is still a largely unresolved issue, causing suffering, disability and high social costs. The search for novel pharmacological targets is therefore a priority. A recent study on postpartal bleeding came to the accidental finding of a possible analgesic action of the oxytocin agonists carbetocin.

Oxytocin is a well known nonapeptide synthesized in the hypothalamus, acting as neurohormone during parturition and the milk ejection reflex. Animal studies have found that descending pathways for oxytocin synthetizing neurons project to the lamina I-II of the spinal cord, where they activate a subpopulation of glutamatergic and GABAergic interneurons. In addition to GABAergic hyperpolarisation, models of oxytocin selectively blocking A-delta and C-fibers have been published. Intrathecal administration of oxytocin prevents long-term potentiation in the dorsal horn, which is thought to be an important mechanism of enhanced central pain processing.

Antagonism to GABAergic and glycinergic neurotransmission mimics many symptoms of inflammatory and neuropathic pain. A loss of synaptic inhibition in the dorsal horn occurs in animal models of experimental pain.

Inhibitory synaptic transmission in the spinal cord dorsal horn use GABA and glycine as their principal fast neurotransmitters. Both of them open the Cl- -channels, which induce postsynaptic hyperpolarisation and impairs the propagation of excitatory potentials on dendrites of neurons. Immunofluorescence studies have revealed abundant glycinergic innervations in the dorsal horn. According to this model, inhibitory GABAergic and glycinergic interneurons in the superficial spinal dorsal horn are key components in the control of pain transmission from the periphery to the brain. The model states that a non-painful stimulation is felt as non painful as long as the synaptic GABAergic and glycinergic inhibition remains intact. A human study on GABAergic modulation of pain by benzodiazepines has been recently performed by our group and was suggestive for an analgesic action. However, these drugs cause sedation and addiction, which strongly limit their clinical usefulness. A pharmacological GABA modulation via the oxytocin receptor may be an attractive alternative, since oxytocin agonists are devoid of these side effects.

Quantitative sensory tests (QST) are used to explore the central processing of painful stimuli in healthy volunteers and patients. They are based on a multimodal and multi-tissue approach, combining different pain modalities applied to different tissues in order to gather sufficient and differentiated information about the human nociceptive system under normal and pathological conditions. QST will be our tool to characterize analgesic efficacy of carbetocin.

Objective

We will test the hypothesis that carbetocin produces analgesia in healthy volunteers, as assessed by multimodal experimental pain testing.

Methods

Intradermal capsaicin injection in the volar forearm is used to create experimental pain an hyperalgesia. The area of hyperalgesia to pinprick and brush allodynia is quantified, and pressure, heat, cold and electrical pain thresholds as well as nociceptive withdrawal reflex thresholds are assessed 30 minutes after capsaicin injection (baseline assessments). Carbetocin 0.1 mg is injected intravenously and the above measurements repeated after 10, 60 and 120 minutes. Blood samples are taken in order to investigate plasma carbetocin levels at 10, 60 and 120 minutes and genetic variants of the oxytocin receptor gene.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • male
  • pain-free
  • written informed consent

Exclusion Criteria

  • chronic pain
  • acute pain at time of testing
  • sign or suspicion of neurological dysfunction at the tested sites
  • intake of opioids
  • intake of benzodiazepines
  • intake of antidepressants
  • intake of anticonvulsants
  • intake of any analgesic drug 48h prior to test
  • known allergy to carbetocin
  • allergy to capsaicin
  • cardiovascular disease
  • asthma bronchiale
  • migraine
  • epilepsy
  • history of liver disease
  • history of renal disease
  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: NCT01918475

Contacts
Contact: Jürg Schliessbach, M.D: 031 632 21 11 juerg.schliessbach@insel.ch

Locations
Switzerland
University Department of Anesthesiology and Pain Therapy, Bern University Hospital Recruiting
Bern, Switzerland, 3010 Bern
Contact: Jürg Schliessbach, M.D.    031 632 21 11    juerg.schliessbach@insel.ch   
Principal Investigator: Pascal Vuilleumier, M.D.         
Sub-Investigator: Jürg Schliessbach, M.D.         
Sub-Investigator: Ulrike Stamer, M.D.         
Sponsors and Collaborators
University Hospital Inselspital, Berne
Investigators
Study Chair: Michele Curatolo, M.D., Ph.D. University Department of Anesthesiology and Pain Therapy, Inselspital Bern, Switzerland
  More Information

Publications:
Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT01918475     History of Changes
Other Study ID Numbers: 140/12, 2013DR1021
Study First Received: August 6, 2013
Last Updated: February 11, 2014
Health Authority: Switzerland: Ethikkommission
Switzerland: Swissmedic

Keywords provided by University Hospital Inselspital, Berne:
randomized controlled trial
placebo controlled trial
cross over trial

Additional relevant MeSH terms:
Hyperalgesia
Somatosensory Disorders
Sensation Disorders
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Analgesics
Oxytocin
Carbetocin
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Oxytocics
Reproductive Control Agents

ClinicalTrials.gov processed this record on July 29, 2014