Condition category
Signs and Symptoms
Date applied
20/08/2007
Date assigned
24/09/2007
Last edited
24/09/2007
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Rolf-Detlef Treede

ORCID ID

Contact details

Institute of Physiology and Pathophysiology
The Johannes Gutenberg University of Mainz
Duesbergweg 6
Mainz
55128
Germany
treede@uni-mainz.de

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

Tr 236/16-2/LTP-Methyl-Lora

Study information

Scientific title

Acronym

LOTEPOLOMETH

Study hypothesis

Long-Term Potentiation (LTP) within the nociceptive system is one of the mechanisms underlying central sensitisation, which accounts for some hyperalgesic pain states in chronic pain patients. In the study we will use a human surrogate model of nociceptive LTP to study the involvement of the GABAergic and the catecholaminergic system in the induction of hyperalgesia following high-frequency electrical stimulation of nociceptive afferents in the skin.

We will study the contribution of GABAA-receptors (by lorazepam, a GABAA-receptor agonist) and receptors of catecholamines (by methylphenidat, a dopamine/noradrenaline re-uptake inhibitor) in plastic changes within the nociceptive system, which occur typically after a tissue injury, but in contrast to a real lesion we mimic an injury by high-frequency electrical stimulation of nociceptive afferents in the skin. This conditioning stimulation will lead to pain to light tactile stimuli (dynamic mechanical allodynia) and to an increase of pain to punctuate mechanical pain stimuli (static mechanical hyperalgesia). Both phenomena can typically been found in a subset of neuropathic pain patients.

Ethics approval

The study was approved by the Local Ethics Committee (Ethikkommission der Landesärztekammer Rheinland-Pfalz) on 15 March 2003 (ref: 837.002.03[3664]) and was conducted in accordance with the declaration of Helsinki, the German Medicines Act (AMG), and the guidelines of the International Conference on Harmonisation (ICH) for Good Clinical Practice (GCP).

Study design

A double-blind, randomized, placebo-controlled, three-way cross-over study.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type

Quality of life

Patient information sheet

Condition

Hyperalgesic pain

Intervention

The effect of 40 mg methylphenidate and 2.5 mg lorazepam orally (p.o.) will be compared to placebo in a three-way cross-over design (placebo-methylphenidate-lorazepam). Sensory changes will be determined by Quantitative Sensory Testing (QST) using non-nociceptive and low-intensity painful mechanical and electrical stimuli.

The QST-protocol consists of mildly painful and non-painful mechanical and electrical stimuli, which were applied in runs alternating between two skin sites on the forearms (a test site and a control site). In addition, we will apply a moderate painful high-frequency electrical stimulation protocol to induce nociceptive LTP (only at the test site). All test stimuli will last between 0.5 - 2 seconds depending on the modality tested.

The QST will be carried out over 30 min before the application of the conditioning stimulus and over 90 min at the beginning and immediately after the stimulus.

Intervention type

Drug

Phase

Not Specified

Drug names

Methylphenidate, Lorazepam

Primary outcome measures

The following outcomes will be assessed based on the sensory changes determined by QST during the intervention:
1. Spread of the area of dynamic allodynia and static hyperalgesia
2. Combined analgesic and anti-hyperalgesic effect to mechanical and electrical stimuli on the site of conditioning stimulation

Secondary outcome measures

The following outcomes will be assessed based on the sensory changes determined by QST during the intervention:
1. Anti-hyperalgesic effect to electrical and mechanical test stimuli
2. Analgesic effect to electrical and mechanical test stimuli
3. Anti-wind up pain, tested by mechanical pinprick stimuli

Overall trial start date

01/10/2006

Overall trial end date

01/10/2007

Reason abandoned

Eligibility

Participant inclusion criteria

1. Healthy volunteers of full age
2. Subject familiarized with the experimental procedure prior to experimentation and had given written informed consent
3. At least a 50% increase of pain to pinprick stimuli and a 25% increase of pain to electrical stimuli following high-frequency electrical stimulation in a screening visit

Participant type

Healthy volunteer

Age group

Adult

Gender

Both

Target number of participants

18

Participant exclusion criteria

1. Skin lesions at the test and/or control site
2. Use of any medication within one day prior to study onset except contraceptives
3. Known hypersensitivity to histamine or methylphenidate and lorazepam and their derivates
4. Any history of allergy or drug hypersensitivity
5. Chronic use of analgesics or Central Nervous System (CNS) active drugs
6. Pregnancy or nursing
7. Any acute or chronic disease

Recruitment start date

01/10/2006

Recruitment end date

01/10/2007

Locations

Countries of recruitment

Germany

Trial participating centre

Institute of Physiology and Pathophysiology
Mainz
55128
Germany

Sponsor information

Organisation

Individual sponsor (Germany)

Sponsor details

c/o Prof Rolf-Detlef Treede
Institute of Physiology and Pathophysiology
The Johannes Gutenberg University of Mainz
Duesbergweg 6
Mainz
55128
Germany
+49 (0)61313925715
treede@uni-mainz.de

Sponsor type

Other

Website

http://www.uni-mainz.de/eng/index.php

Funders

Funder type

Other

Funder name

German Research Foundation (Deutsche Forschungsgemeinschaft) (Grant ref: Tr236/16-2)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes