Improvement the Anti-migraine Treatment Efficacy by Tailoring the Drug to Individual's Pain Modulation Profile

• To delineate brain mechanisms that subserve endogenous analgesic (EA) in the healthy state.
• To identify alterations in mechanisms supporting EA in chronic pain (migraine) and their therapeutic relevance.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: duloxetine

Detailed Description

The proposed research will use psychophysics and multiparametric MRI to (i) delineate the brain mechanisms that subserve and regulate endogenous analgesia (EA)in the healthy state and (ii) to identify alterations in mechanisms supporting EA in chronic pain and their therapeutic relevance. In both healthy subjects and chronic pain patients, EA will be probed using the DNIC (diffuse noxious inhibitory controls) and offset analgesia paradigms. Functional MRI will examine activation of brainstem mechanisms important in EA, while both functional and structural connectivity analyses will assess the regulation of these brainstem mechanisms by cerebral cortical regions involved in attention and affect. One pathological painful condition, migraine, will be examined since it allows changes in EA associated with chronic pain to be investigated between episodes of pain. Finally, EA and EA associated structural and functional parameters will be used to predict the efficacy of one compound, amitriptyline, to treat migraine in individual patients. Taken together, the proposed research will provide substantial insights into basic mechanisms supporting and regulating EA and can provide a foundation for mechanism-based individualized choice of therapy that may benefit all chronic pain patients.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Haifa, Israel
    • MRI center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• healthy females
• migaine females
• ages 18-50
• for migraineurs: >4 attacks/month

Exclusion Criteria:

• any migraine preventive treatment received during last 3 months or prior treatment with amytriptiline
• other chronic pain conditions
• psychiatric, other neurological diseases, language barrier or cognitive dysfunction
• Patients and controls will be asked to withdraw from any pain-relieving medications for 24 hours before the testing. The tests will be performed interictally atleast 2 days after the last attack.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; migraine patients to receive placebo treatment	Drug: duloxetine; duloxetine 60mg once a day for 5 weeks
Active Comparator: duloxetine; migraine patients to receive duloxetine	Drug: duloxetine; duloxetine 60mg once a day for 5 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Distinguish between two endogenous pain modulation mechanisms	2 year

Secondary Outcome Measures

Outcome Measure	Time Frame
To charcterize functional and structural neuroanatomical correlates of pain modulation profile and it's relevance for predicting the duloxetine efficacy in migraine	3 years

Collaborators and Investigators

• Sponsor: Rambam Health Care Campus

Study record dates

Study Major Dates

• Study Start: December 1, 2011
• Primary Completion (Actual): July 1, 2014
• Study Completion (Actual): July 1, 2014

Study Registration Dates

• First Submitted: November 9, 2011
• First Submitted That Met QC Criteria: November 10, 2011
• First Posted (Estimate): November 11, 2011

Study Record Updates

• Last Update Posted (Estimate): September 17, 2015
• Last Update Submitted That Met QC Criteria: September 16, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: fMRI; endogenous pain modulation; migraine; duloxetine; preventive migraine treatment
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: 0462-10-RMB.CTIL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No