Effects of Pregabalin on Mechanical Hyperalgesia

Condition(s) targeted: Tactile Hyperalgesia; Neuropathic Pain

Intervention: Pregabalin (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Professional Associations Clinic Bergmannsheil

Official(s) and/or principal investigator(s):
Christoph Maier, Prof. MD., Study Director, Affiliation: Professional Associations Clinic Bergmannsheil , Dept. of Pain Therapy

Overall contact:
Christoph Maier, Prof. MD, Phone: +49 (0)234 - 302 - 6366, Email: christoph.maier@rub.de

The aim of this randomized placebo-controlled study is to evaluate the effects of analgetics for neuropathic pain on mechanical hyperalgesia as a kind of evoked pain. Therefore the number of responders and non-responders on pregabalin will be evaluated in respect of mechanical hyperalgesia (stimulus-response-function (SRF) on static punctual stimuli evoking pain determined via pinprick). The hypothesis is that in the placebo group the amount of non-responders is increased.

Official title: Effects of Pregabalin on Mechanical Hyperalgesia - EPOM

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: number of responders and non-responders in respect of mechanical hyperalgesia (stimulus-response-function (SRF) on static punctual stimuli evoking pain determined via pinprick)

Secondary outcome:

Degree of mechanical hyperalgesia

Ongoing pain (numerical rating scale)

Neuropathic Pain Symptom Inventory score

Additional QST (qualitative sensory testing) variable CDT = cold detection threshold,

Additional QST (qualitative sensory testing) variable HDT = heat detection threshold

Additional QST (qualitative sensory testing) variable TSL = thermal sensory limen

Additional QST (qualitative sensory testing) variable PHS = number of paradoxical heat sensations during the TSL Procedure

Additional QST (qualitative sensory testing) variable CPT = cold pain threshold

Additional QST (qualitative sensory testing) variable HPT = heat pain threshold

Additional QST (qualitative sensory testing) variable MDT = mechanical detection threshold

Additional QST (qualitative sensory testing) variable MPT = mechanical pain threshold

Additional QST (qualitative sensory testing) variable ALL = dynamic mechanical allodynia

Additional QST (qualitative sensory testing) variable WUR = windup ratio

Additional QST (qualitative sensory testing) variable VDT = vibration detection threshold

Additional QST (qualitative sensory testing) variable PPT = pressure pain threshold)

Detailed description: This randomized controlled trial is intended to be the first in a series of trials that will assess the efficacy of drugs, which relieve neuropathic pain, on stimulus-evoked pain (here: mechanical hyperalgesia to static punctate stimuli). Most drugs in this class (e. g. Gabapentin or NMDA receptor inhibitors) have NNT beyond 3 in patients with chronic pain, due to a response rate of 30 to 50 %. One potential reason for this low overall efficacy might be the presence of different pathophysiological mechanisms in subgroups of patients, who suffer from the same disease (e. g. postherpetic neuralgia, diabetic neuropathy). These mechanisms may include central sensitization on one hand and peripheral degeneration of afferent fibers on the other hand.

In this trial, we will use a battery of mechanical and thermal Quantitative Sensory Tests (QST), using non-nociceptive and low-intensity painful stimuli, to identify a subgroup of patients with mechanical hyperalgesia. To overcome the well-known low response rate in trials with neuropathic pain patients, an enriched design comparing active drugs with placebo will be performed, including only patients with high intensity of on-going pain in combination with mechanical hyperalgesia as sequelae of different, but well defined neurological disorders. The blinded phase of the trial will be restricted to so-called responders, i. e. patients with a clinically meaningful pain reduction of at least 30% in the primary end point (mechanical hyperalgesia). The second objective of this trial is to evaluate, whether the anti-hyperalgesic effect of the active drug is dependent on the QST profile.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

Recruitment:

- Age above 18 years;

- Neuropathic pain of at least 4/10 for at least 6 months;

- Mechanical hyperalgesia;

- One of the following diagnoses: peripheral nerve lesion, plexus lesion, radicular

lesion, spinal lesion, polyneuropathy, postzosteric neuralgia;

- No nerve block or other interventional treatment for at least 4 weeks;

- Constant medication for at least 4 weeks;

- Signed informed consent;

- WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L

or equivalent units of HCG) within 72 hours prior to the start of study medication;

- Women of childbearing potential (WOCBP) must be using an adequate method of

contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study in such a manner that the risk of pregnancy is minimized.

Enrolment open titration:

- All principal inclusion criteria at recruitment

- Relevant mechanical hyperalgesia: SRF affected/control at least 2. 0 with a minimal

SRF of 0. 8.

Enrolment double-blind phase:

- At least 30% reduction in mechanical hyperalgesia (SRF) in the open titration;

- WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L

or equivalent units of HCG) within 72 hours prior to the start of study medication;

- Women of childbearing potential (WOCBP) must be using an adequate method of

contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study (see above recruitment).

Exclusion Criteria:

- Anaphylaxis on the active component or any other component of Lyrica or the placebo

(Lyrica®: pregabalin, lactose-monohydrate, corn starch, talcum; capsule shells: gelatine, titanium dioxide (E 171), natriumdodecylsulfat, high dispersive siliciumdioxide, purified water; ink: shellac, black iron(II,III)-oxide (E 172), propyleneglycol, kaliumhydroxide; additionally in placebo: microcrystalline cellulose, sucrose octaacetate, magnesium stearate)

- Intake of gabapentin or pregabalin within the last 4 weeks prior to recruitment

- Any surgery within the last two months or any scheduled surgery within the study

period (20 weeks);

- Concurrent unstable disease involving any system, e. g. advanced carcinoma, acute

myocardial infarction, renal failure, or any other condition that in the opinion of the Investigator would deem the patient unsuitable for the study;

- History of cerebral vascular or other cerebral disease;

- Concurrent chronic or acute pain of other origin (osteoarthritis), which is not

treated effectively

- Concurrent severe mental deficit, e. g. psychiatric disorders as defined by DSM IV

including schizophrenia, mood disorders, organic brain syndrome, psychotic/delusional disorders, serious psychosis;

- Concurrent serious neurological disease, e. g. dementia, multiple sclerosis, or any

other disease that would have impact on the ability of the patient to give their consent for the participation in the study or influences the pain perception;

- Concurrent atrioventricular block second degree or higher

- Concurrent renal failure (CLcr < 30 ml/min)

- Concurrent hereditary galactose-intolerance

- Concurrent lapp-lactase insufficiency

- Concurrent glucose-galactose-malabsorption

- Concurrent sub-optimal stabilized Diabetes Mellitus (Hb1Ac > 12%)

- Clinical apparent overdosage of opioids or psychopharmaca

- Recent history (6 months) or current evidence of alcohol or drug abuse;

- Participation in any other investigational drug or therapy study within the previous

90 days;

- Women who are pregnant or breastfeeding;

- Women with a positive pregnancy test on enrollment or prior to study drug

administration;

- Women of childbearing potential who are unwilling or unable to use an acceptable

method to avoid pregnancy for the entire study period and for up to 4 weeks after the study. Women practicing abstinence should use a reliable method of contraception (except birth control pills) if they choose to become sexually active during the study.

Christoph Maier, Prof. MD, Phone: +49 (0)234 - 302 - 6366, Email: christoph.maier@rub.de

Dept. of Neurology, University of Ulm, Ulm 89075, Germany; Recruiting
Bernhard G. Landwehrmeyer, Prof. MD, Phone: +49(0)731-500-50950, Email: bernhard.landwehrmeyer@uni-ulm.de
Bernhard G. Landwehrmeyer, Prof. MD, Principal Investigator
Roland Klug, MD, Sub-Investigator

Dept. of Anaesthesia and Transfusion Medicine, University of Tuebingen, Tuebingen 72076, Germany; Not yet recruiting
Sabine Bredanger, MD, Phone: +49(0)7071-29-85612, Email: sabine.bredanger@med.uni-tuebingen.de
Sabine Bredanger, MD, Sub-Investigator
Klaus Unertl, Prof. MD, Principal Investigator

Interdisciplinary Dept. of Pain Management, Dept. of Anaesthesiology, Ludwig-Maximilians-University, Munich 81377, Germany; Not yet recruiting
Shanhnaz C Azad, PD MD, Phone: +49(0)89-7094-4464, Email: Shahnaz.Azad@med.uni-muenchen.de
Shanhaz C Azad, PD MD, Principal Investigator
Meike Lauchert, MD, Sub-Investigator
Volker Huge, MD, Sub-Investigator

Dept. of Anaesthesiology, University Hospital of Erlangen, Erlangen 91054, Germany; Not yet recruiting
Wolfgang Koppert, PD MD, Phone: +49(0)9131-85-32901, Email: koppert@kfa.imed.uni-erlangen.de
Wolfgang Koppert, PD MD, Principal Investigator

Insitute of Physiology and Experimental Pathophysiology, Erlangen 91054, Germany; Not yet recruiting
Christian Maihöfner, MD, Phone: +49(0)9131-85-22498, Email: christian.maihoefner@neuro.imed.uni-erlangen.de
Christian Maihöfner, MD, Principal Investigator

Dept. of Neurology, Universtity Hospital TU Munich, Munich 81675, Germany; Not yet recruiting
Thomas R Toelle, Prof. MD, Phone: +49(0)89-4140-4603, Email: toelle@neuro.med.tu-muenchen.de
Thomas R Toelle, Prof. MD, Principal Investigator
Michael Valet, MD, Sub-Investigator
Till Sprenger, MD, Sub-Investigator
Dorothee Nietzsche, MD, Sub-Investigator
Christoph Bach, MD, Sub-Investigator
Achim Berthele, PD MD, Sub-Investigator

University Hospital of Duesseldorf, Dept. of Paintherapy, Dept. of Anaesthesiology, Duesseldorf 40225, Germany; Not yet recruiting
Rainer Freynhagen, MD, Phone: +49(0)211-81-19157, Email: freynhagen@med.uni-duesseldorf.de
Rainer Freynhagen, MD, Principal Investigator
Andrea Schmitz, MD, Sub-Investigator
Peter Busche, MD, Sub-Investigator

Berufsgenossenschaftliche Kliniken Bergmannsheil, Dept. of Anaesthesiology, Intensive Care and Pain Therapy, Dept. of Pain Therapy, Bochum 44789, Germany; Recruiting
Christhop Maier, Prof. MD, Phone: +49(0)234-302-6366, Email: christoph.maier@rub.de
Christoph Maier, Prof. MD, Principal Investigator
Andrea Scherens, MD, Sub-Investigator

Anesthesiology and Surgical Intensive Care Medicine, University of Muenster, Muenster 48149, Germany; Not yet recruiting
Esther Pogatzki-Zahn, PD MD, Phone: +49(0)251-834-7258, Email: pogatzki@anit.uni-muenste.de
Esther Pogatzki-Zahn, PD MD, Principal Investigator

DRK - Pain Centre Mainz, Mainz 55131, Germany; Recruiting
Susann Seddigh, MD, Phone: +49(0)6131-988510, Email: susann.seddigh@drk-schmerz-zentrum.de
Susann Seddigh, MD, Principal Investigator

Health Care Centre, Dept. of Neurology, Johannes Gutenberg University of Mainz, Mainz 55101, Germany; Recruiting
Frank Birklein, Prof. MD, Phone: +49(0)6131-17-3270, Email: birklein@neurologie.klinik.uni-mainz.de
Frank Birklein, Prof. MD, Principal Investigator
Christian Gerber, MD, Sub-Investigator
Roman Rolke, MD, Sub-Investigator

Dept. of Neurology, Neurological Section, Pain Research and Therapy, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel 24105, Germany; Recruiting
Ralf Baron, Prof. MD, Phone: +49(0)431-597-1809, Email: r.baron@neurologie.uni-kiel.de
Ralf Baron, Prof. MD, Principal Investigator
Andreas Binder, MD, Sub-Investigator
Janne Ludwig, MD, Sub-Investigator
J Schattschneider, MD, Sub-Investigator

Neurological Hospital, University of Wuerzburg, Wuerzburg 97080, Germany; Not yet recruiting
Claudia Sommer, Prof. MD, Phone: +49(0)931-201-23763, Email: sommer@mail.uni-wuerzburg.de
Claudia Sommer, Prof. MD, Principal Investigator
Nurcan Uceler, MD, Sub-Investigator

Pain Therapy, Dept. of Anaesthesiology and Intensive Care Medicine, University of Cologne, Cologne 50924, Germany; Not yet recruiting
Frank Petzke, MD, Phone: +49(0)221-478-3627, Email: frank.petzke@uni-koeln.de
Thorsten Giesecke, MD, Sub-Investigator
Frank Petzke, PD MD, Principal Investigator

Pain Therapy, Dept. of Anaestesiology and Intensive Care Medicine, Clinical Medicine Mannheim, University of Heidelberg, Mannheim 68167, Germany; Not yet recruiting
Ulrike Friess, MD, Phone: +49(0)621-383-2608, Email: ulrike.friess@anaes.ma.uni-heidelberg.de
Ulrike Friess, MD, Principal Investigator

Dept. of Neuroradiology, Neurological Health Care Center, University Hospital of Heidelberg, Heidelberg 69120, Germany; Not yet recruiting
Christoph Stippich, PD MD, Phone: +49(0)6221-56-39607, Email: christoph.stippich@med.uni-heidelberg.de
Christoph Stippich, PD MD, Principal Investigator

Neurological University Hospital, University of Freiburg, Freiburg 79106, Germany; Not yet recruiting
Ingolf C Bötefür, MD, Phone: +49(0)761-270-5001, Email: botefur@nz.ukl.uni-freiburg.de
Ingolf C Bötefür, MD, Principal Investigator

German Network Neuropathic Pain

German Ministry of Education and Research

German Federal Institute for Drugs and Medical Devices

Ethics Committee, Medical Department of the Ruhr-University Bochum

Starting date: July 2006
Ending date: April 2008
Last updated: April 4, 2007