Pharmacological modulation of heterosynaptic LOng-TErm POtentiation in humans by ONdansetron and DExtromethorphan

ISRCTN ISRCTN38944269
DOI https://doi.org/10.1186/ISRCTN38944269
Secondary identifying numbers Tr 236/16-2/LTP-Ondan-Dex
Submission date
03/11/2006
Registration date
04/01/2007
Last edited
04/01/2007
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Signs and Symptoms
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Rolf-Detlef Treede
Scientific

Institute of Physiology and Pathophysiology
Johannes Gutenberg-University Mainz
Duesbergweg 6
Mainz
55128
Germany

Email treede@uni-mainz.de

Study information

Study designThe trial was designed as a double blind, randomised and placebo-controlled three-way cross-over study (Placebo-Dextromethrophan-Ondansetron).
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Scientific title
Study acronymLOTEPODEON (LOng-TErm POtentiation DExtromethorphan ONdansetron)
Study objectivesLong-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 NMDA-receptors and 5-HT3-receptors in the induction of hyperalgesia following high-frequency electrical stimulation of nociceptive afferents in the skin.

We will study the contribution of NMDA- and 5-HT3 receptors 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(s)The study was approved by the local ethics committee (Ethikkommission der Landesärztekammer Rheinland-Pfalz; 15th March, 2003, reference number: 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).
Health condition(s) or problem(s) studiedHyperalgesic pain states in chronic pain patients
InterventionThe effect of 150 mg dextromethorphan and 16 mg ondansetron orally (p.o.) will be compared to placebo in a three-way cross-over design. Sensory changes will be determined by Quantitative Sensory Testing (QST) using non-nociceptive and low-intensity painful mechanical and electrical stimuli.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Specified
Drug / device / biological / vaccine name(s)Dextromethrophan and Ondansetron
Primary outcome measure1. Spread of the area of dynamic allodynia and static hyperalgesia
2. Combined analgesic and anti-hyperalgesic effect to mechancial and electrical stimuli on the site of conditioning stimulation
Secondary outcome measures1. Anti-hyperalgesic effect to electrical and mechanical test stimuli
2. Analgesic effect to electrical and mechanical test stimuli
3. Anti-wind up
Overall study start date01/07/2005
Completion date31/12/2006

Eligibility

Participant type(s)Healthy volunteer
Age groupAdult
SexNot Specified
Target number of participants18
Key inclusion criteria1. Healthy volunteers of full age
2. Subject familiarised 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
Key exclusion criteria1. 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 to dextromethorphan and ondansetron 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
Date of first enrolment01/07/2005
Date of final enrolment31/12/2006

Locations

Countries of recruitment

  • Germany

Study participating centre

Institute of Physiology and Pathophysiology
Mainz
55128
Germany

Sponsor information

Individual Sponsor (Germany)
Other

Prof. Dr. Rolf-Detlef Treede
Institute of Physiology and Pathophysiology
Johannes Gutenberg-University Mainz
Duesbergweg 6
Mainz
55128
Germany

Phone +49 (0)61313925715
Email treede@uni-mainz.de

Funders

Funder type

Research organisation

The study is supported by a grant from the German Research Foundation (Deutsche Forschungsgemeinschaft) (Germany) (Grant: Tr236/16-2)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan