Phantom Limb Pain Triggered by Micturition

• ClinicalTrials.gov Identifier: NCT03855930
• Recruitment Status: Unknown
• First Posted: February 27, 2019
• Last Update Posted: February 27, 2019
• Sponsor: Loewenstein Hospital
• Collaborator: Tel Aviv University
• Information provided by (Responsible Party): Loewenstein Hospital

Study Description

Brief Summary:

Phantom Limb Pain ( PLP) is pain that is perceived and referred to a region of the body that is no longer present. in most patients, severity and frequency of phantom pain attacks gradually decrease over several weeks to 2 years following amputation, however in 5-10% significant pain remains a serious problem.

It has been hypothesized, that deprivation of various inputs from the limbs to the brain cause an abnormal neuro-signature to be produced generating cortical maladaptive neuroplasticity and reorganization. Areas representing the amputated body part are taken over by neighboring representational zones in both the somatosensory and motor cortex generating pain in absence of stimuli.

A seminal paper published by Lotze et al "Phantom movements and pain: a functional magnetic resonance imaging (fMRI) study in upper limb amputees. - participants had to pucker their lips at a metronome-paced speed while functional magnetic resonance images were taken. Only in amputees with phantom-limb pain did a shift of the mouth representation into the hand representation occur; those without pain and the healthy control do not display a similar shift.

Scarce reports have been made on a similar phenomenon- micturition induced lower limb phantom pain.

We speculate that a similar maladaptive central nerve system (CNS) plasticity in which this genital representation would invade cortical areas with somatotopic affiliation to the lower extremity could be implicated in the pathophysiology of this phenomenon.

Condition or disease	Intervention/treatment
Phantom Limb Pain	Diagnostic Test: functional MRI

Detailed Description:

The present study was there for devised to examine this hypothesis utilizing fMRI imaging of temporo-spatial cortical activation during micturition and pain generation.

We hypothesis that in amputees with phantom-limb pain a shift of the genital representation into the leg representation will occur; and will be demonstrated as an uni-hemispheral activity on fMRI during micturition and pain suggesting maladaptive CNS plasticity. Moreover, we speculate that healthy volunteers will not display a similar shift.

During the study, standard motor and sensory paradigms will be performed to establish anatomical and functional patterns in the non-painful state. The patient will then be asked to urinate (to an external collecting tube system).

All anatomical data will be examined by a certified clinical imaging specialist to exclude concomitant brain pathology.

Study population -

1. 10 Patients with chronic post amputation micturition induced PLP.All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria.
2. 10 Patients with chronic post amputation with PLP and without post amputation micturition induced PLP All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria.
3. 10 healthy volunteers

FMRI data analysis signifying, statistically significant uni-spatial voxel activity during micturition, in the study group

Study Design

• Study Type: Observational
• Estimated Enrollment: 30 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Phantom Limb Pain Triggered by Micturition, An Functional Magnetic Resonance Imaging (FMRI) Study in Lower Limb Amputees
• Estimated Study Start Date: February 25, 2019
• Estimated Primary Completion Date: February 2, 2020
• Estimated Study Completion Date: February 2, 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
micturition induced PLP; 10 Patients with chronic post amputation micturition induced PLP.All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria. All patients will go through functional MRI study	Diagnostic Test: functional MRI; During the study, standard motor and sensory paradigms will be performed to establish anatomical and functional patterns in the non-painful state. The patient will then be asked to urinate (to an external collecting tube system).
non micturition induced PLP; 10 Patients with chronic post amputation with PLP and without post amputation micturition induced PLP All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria.All patients will go through functional MRI study	Diagnostic Test: functional MRI; During the study, standard motor and sensory paradigms will be performed to establish anatomical and functional patterns in the non-painful state. The patient will then be asked to urinate (to an external collecting tube system).
healthy volunteers; 10 healthy volunteers. All patients will go through functional MRI study	Diagnostic Test: functional MRI; During the study, standard motor and sensory paradigms will be performed to establish anatomical and functional patterns in the non-painful state. The patient will then be asked to urinate (to an external collecting tube system).

Outcome Measures

Primary Outcome Measures :

1. FMRI data analysis [ Time Frame: 18 months ]
   FMRI data analysis signifying, statistically significant uni-spatial voxel activity during micturition, in the study groups.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

1. 10 Patients with chronic post amputation micturition induced PLP.All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria.
2. 10 Patients with chronic post amputation with PLP and without post amputation micturition induced PLP All subjects must fulfill all of the inclusion criteria and meet none of the exclusion criteria.
3. 10 healthy volunteers

Criteria

Inclusion Criteria:

• 9 months or more post amputation, no anatomical stump pathology
• Ambulatory and to comply with study protocol
• Suffering from significant pain (VAS>??). pain level has plateaued for at lest 2 months prior to enrolment.
• Pain is perceived to be located in the missing limb
• Pain level is brought up or increases (by at least 3 VAS points) by micturition.
• Maneuvers causing abdominal pressure elevation do not generate similar symptoms.
• Subject received an explanation about the nature of the study and agrees to provide written informed consent
• Subject is capable and willing to follow all study-related procedures

Exclusion Criteria:

• Any condition inhibiting MRI study (e.g.Pacemakers or other implantable neurostimulators, ….)
• Subject has any condition, which precludes compliance with study instructions.
• Subject suffers from life threatening conditions
• Anatomical limitations that would prevent successful FMRI study
• Other medical conditions precluding FMRI study - e.g., claustrophobia
• Women gender- due to problematic usage of external urinating device during fMRI study

Contacts and Locations

Contacts

Contact: Motti Ratmansky, MD; +972097709029 ext 9140; mottir@clalit.org.il

Contact: Amir Haim, MD; +972549765999; amirhaim@gmail.com

Locations

Israel

Loewenstein Rehabilitation Center

Ra'anana, Israel, 43100

Loewenstein Rehabilitation Center

Raanana, Israel

Sponsors and Collaborators

Loewenstein Hospital

Tel Aviv University

Investigators

• Principal Investigator: Motti Ratmansky, MD; Loewenstein Rehabilitation Hospital

More Information

Publications of Results:

Michels L, Blok BF, Gregorini F, Kurz M, Schurch B, Kessler TM, Kollias S, Mehnert U. Supraspinal Control of Urine Storage and Micturition in Men--An fMRI Study. Cereb Cortex. 2015 Oct;25(10):3369-80. doi: 10.1093/cercor/bhu140. Epub 2014 Jun 26.

Flor H. Phantom-limb pain: characteristics, causes, and treatment. Lancet Neurol. 2002 Jul;1(3):182-9. Review.

Shy M, Fung S, Boone TB, Karmonik C, Fletcher SG, Khavari R. Functional magnetic resonance imaging during urodynamic testing identifies brain structures initiating micturition. J Urol. 2014 Oct;192(4):1149-54. doi: 10.1016/j.juro.2014.04.090. Epub 2014 Apr 21.

• Responsible Party: Loewenstein Hospital
• ClinicalTrials.gov Identifier: NCT03855930
• Other Study ID Numbers: 0012-18-LOE
• First Posted: February 27, 2019
• Last Update Posted: February 27, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Phantom Limb; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Pain, Postoperative; Postoperative Complications; Pathologic Processes; Pain