Effects of Pregabalin on Mechanical Hyperalgesia

April 4, 2007 updated by: Professional Associations Clinic Bergmannsheil

Effects of Pregabalin on Mechanical Hyperalgesia - EPOM

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

120

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Bochum, Germany, 44789
        • Recruiting
        • Berufsgenossenschaftliche Kliniken Bergmannsheil, Dept. of Anaesthesiology, Intensive Care and Pain Therapy, Dept. of Pain Therapy
        • Contact:
        • Principal Investigator:
          • Christoph Maier, Prof. MD
        • Sub-Investigator:
          • Andrea Scherens, MD
      • Cologne, Germany, 50924
        • Not yet recruiting
        • Pain Therapy, Dept. of Anaesthesiology and Intensive Care Medicine, University of Cologne
        • Contact:
        • Sub-Investigator:
          • Thorsten Giesecke, MD
        • Principal Investigator:
          • Frank Petzke, PD MD
      • Duesseldorf, Germany, 40225
        • Not yet recruiting
        • University Hospital of Duesseldorf, Dept. of Paintherapy, Dept. of Anaesthesiology
        • Contact:
        • Principal Investigator:
          • Rainer Freynhagen, MD
        • Sub-Investigator:
          • Andrea Schmitz, MD
        • Sub-Investigator:
          • Peter Busche, MD
      • Erlangen, Germany, 91054
        • Not yet recruiting
        • Dept. of Anaesthesiology, University Hospital of Erlangen
        • Contact:
        • Principal Investigator:
          • Wolfgang Koppert, PD MD
      • Erlangen, Germany, 91054
        • Not yet recruiting
        • Insitute of Physiology and Experimental Pathophysiology
        • Contact:
        • Principal Investigator:
          • Christian Maihöfner, MD
      • Freiburg, Germany, 79106
        • Not yet recruiting
        • Neurological University Hospital, University of Freiburg
        • Contact:
        • Principal Investigator:
          • Ingolf C Bötefür, MD
      • Heidelberg, Germany, 69120
        • Not yet recruiting
        • Dept. of Neuroradiology, Neurological Health Care Center, University Hospital of Heidelberg
        • Contact:
        • Principal Investigator:
          • Christoph Stippich, PD MD
      • Kiel, Germany, 24105
        • Recruiting
        • Dept. of Neurology, Neurological Section, Pain Research and Therapy, Universitätsklinikum Schleswig-Holstein, Campus Kiel
        • Contact:
        • Principal Investigator:
          • Ralf Baron, Prof. MD
        • Sub-Investigator:
          • Andreas Binder, MD
        • Sub-Investigator:
          • Janne Ludwig, MD
        • Sub-Investigator:
          • J Schattschneider, MD
      • Mainz, Germany, 55101
        • Recruiting
        • Health Care Centre, Dept. of Neurology, Johannes Gutenberg University of Mainz
        • Contact:
        • Principal Investigator:
          • Frank Birklein, Prof. MD
        • Sub-Investigator:
          • Christian Gerber, MD
        • Sub-Investigator:
          • Roman Rolke, MD
      • Mainz, Germany, 55131
      • Mannheim, Germany, 68167
        • Not yet recruiting
        • Pain Therapy, Dept. of Anaestesiology and Intensive Care Medicine, Clinical Medicine Mannheim, University of Heidelberg
        • Contact:
        • Principal Investigator:
          • Ulrike Friess, MD
      • Muenster, Germany, 48149
        • Not yet recruiting
        • Anesthesiology and Surgical Intensive Care Medicine, University of Muenster
        • Contact:
        • Principal Investigator:
          • Esther Pogatzki-Zahn, PD MD
      • Munich, Germany, 81377
        • Not yet recruiting
        • Interdisciplinary Dept. of Pain Management, Dept. of Anaesthesiology, Ludwig-Maximilians-University
        • Contact:
        • Principal Investigator:
          • Shanhaz C Azad, PD MD
        • Sub-Investigator:
          • Meike Lauchert, MD
        • Sub-Investigator:
          • Volker Huge, MD
      • Munich, Germany, 81675
        • Not yet recruiting
        • Dept. of Neurology, Universtity Hospital TU Munich
        • Contact:
        • Principal Investigator:
          • Thomas R Toelle, Prof. MD
        • Sub-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
      • Tuebingen, Germany, 72076
        • Not yet recruiting
        • Dept. of Anaesthesia and Transfusion Medicine, University of Tuebingen
        • Contact:
        • Sub-Investigator:
          • Sabine Bredanger, MD
        • Principal Investigator:
          • Klaus Unertl, Prof. MD
      • Ulm, Germany, 89075
        • Recruiting
        • Dept. of Neurology, University of Ulm
        • Contact:
        • Principal Investigator:
          • Bernhard G. Landwehrmeyer, Prof. MD
        • Sub-Investigator:
          • Roland Klug, MD
      • Wuerzburg, Germany, 97080
        • Not yet recruiting
        • Neurological Hospital, University of Wuerzburg
        • Contact:
        • Principal Investigator:
          • Claudia Sommer, Prof. MD
        • Sub-Investigator:
          • Nurcan Uceler, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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 Measures

Outcome Measure
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Professional Associations Clinic Bergmannsheil

Collaborators

German Federal Ministry of Education and Research

Investigators

  • Study Director: Christoph Maier, Prof. MD., Professional Associations Clinic Bergmannsheil , Dept. of Pain Therapy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Study Completion (ANTICIPATED)

April 1, 2008

Study Registration Dates

First Submitted

April 3, 2006

First Submitted That Met QC Criteria

April 3, 2006

First Posted (ESTIMATE)

April 4, 2006

Study Record Updates

Last Update Posted (ESTIMATE)

April 5, 2007

Last Update Submitted That Met QC Criteria

April 4, 2007

Last Verified

April 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2005-000411-10
  • BfArM61-3910-4030984
  • 4478944789
  • EV2005-2509

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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