Pain Prevention and Treatment Through the Enhancement of the Anti-nociceptive Component of Pain Modulation Profiles

• ClinicalTrials.gov Identifier: NCT02020122
• Recruitment Status: Completed
• First Posted: December 24, 2013
• Last Update Posted: October 4, 2017
• Sponsor: Rambam Health Care Campus
• Information provided by (Responsible Party): d_yarnitsky, Rambam Health Care Campus

Study Description

Brief Summary:

To utilize the plasticity of the central pain pathways in order to (i) shift individuals with a pro-nociceptive pain modulation profile towards an anti-nociceptive one, and (ii) assess its relevance in minimizing pain-derived morbidity.

Condition or disease	Intervention/treatment	Phase
Pain	Drug: Duloxetine; Drug: Pregabalin; Drug: Placebo	Not Applicable

Detailed Description:

In the project proposed here our main aim is to shift pain modulation towards anti-nociception as a novel approach to pain prevention and treatment. Our first hypothesis is that individual's modulation profile, when not anti-nociceptive, can be pharmacologically shifted into being anti-nociceptive. We assert (the first hypothesis) that such shift can be optimized by coupling the drug's mode of action with the individual's pain modulation profile; based on limited available data, it is suggested that less efficient inhibitory pain modulation will be modified best by serotonin-norepinephrine reuptake inhibitors (SNRIs), whereas enhanced facilitatory modulation will be modified best by Ca++ channel ligands. Pain modulation will be assessed by psychophysical tools, and will include dynamic tests of pain modulation. The conditioned pain modulation (CPM) test protocol will be used for assessing pain inhibition, and the temporal summation (TS) test protocol will be used for assessment of pain facilitation. Our second hypothesis is that SNRIs will be most efficacious in shifting individuals into being antinociceptive if these individuals had lower activation of the anterior brain pain network in the CPM test paradigm. In turn, Ca++ channel ligands will be most efficacious for individuals showing enhanced activation of the posterior pain network sites in response to the TS test protocol. Our third hypothesis is that an anti-nociceptive pain modulation profile protects individuals from acquiring pain. The model we chose for this study is surgery for coronary artery bypass grafting (CABG). Individuals scheduled for surgery, who are pain free, will be assigned to 3 arms - (1) duloxetine (DUL) (SNRI), (2) pregabalin (PGB) (Ca++ channel ligand) and (3) placebo. Drugs will be taken for 48 hours prior to surgery in a double-blind non cross-over parallel design. Pain modulation will be assessed before treatment, 2-4 hours prior to surgery and at its end, 6 weeks before surgery. Post operative acute and chronic pain will be assessed up to 2 month after surgery.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 5 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Actual Study Start Date: January 2014
• Actual Primary Completion Date: January 2015
• Actual Study Completion Date: January 2015

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Duloxetine; DUL 60mg x once a day x 2 days. This arm will also take 2 non-active placebo x once a day x 2 days	Drug: Duloxetine; duloxetine 60mg; Drug: Placebo; non active placebo
Active Comparator: Pregabalin; PGB 150mg x twice a day x 2 days	Drug: Pregabalin; pregabalin 150mg
Placebo Comparator: Placebo; Non active placebo x twice a day x 2 days	Drug: Placebo; non active placebo

Outcome Measures

Primary Outcome Measures :

1. The changes in pain response after administration of duloxetine and pregabalin [ Time Frame: 3 years ]
   The changes in the excitatory and inhibitory pain modulation responses (assessed by temporal summation and conditioned pain modulation) will be examined before and after the administration of duloxetine and pregabalin in the set of pre and post coronary artery bypass grafting surgery.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Otherwise healthy, age 18-75.

Exclusion Criteria:

• Regular use of analgesia for any purpose, including SNRIs, gabapentins, COX inhibitors.
• Presence of diagnosed chronic pain disorders, psychiatric disorders, cognitive and /or neurological deficit.
• Inability to give informed consent, communicate and understand the purpose and instructions of this study.
• Pregnant or nursing women.

Contacts and Locations

Locations

Israel

Rambam Health Care Campus

Haifa, Israel

Sponsors and Collaborators

Rambam Health Care Campus

Investigators

• Principal Investigator: David Yarnitsky, Professor; Rambam Health Care Campus

More Information

• Responsible Party: d_yarnitsky, Professor, Head of Neurology Deapartment, Rambam Health Care Campus
• ClinicalTrials.gov Identifier: NCT02020122
• Other Study ID Numbers: 0472-13-RMB.CTIL
• First Posted: December 24, 2013
• Last Update Posted: October 4, 2017
• Last Verified: October 2017

Keywords provided by d_yarnitsky, Rambam Health Care Campus:

endogenous pain modulation; coronary artery bypass grafting; quantitative sensory testings; duloxetine; pregabalin; preemptive treatment

Additional relevant MeSH terms:

Pregabalin; Duloxetine Hydrochloride; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anticonvulsants; Calcium Channel Blockers; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Calcium-Regulating Hormones and Agents; Anti-Anxiety Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin and Noradrenaline Reuptake Inhibitors; Neurotransmitter Uptake Inhibitors; Neurotransmitter Agents; Antidepressive Agents; Dopamine Agents