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
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