Clinical trial NCT00304850: Polyamine-free Diet to Prevent Post Surgery Hyperalgesia
Official title: Efficacy of a Polyamine-free Diet Associated or Not With Ketamine on Early and Late Hyperalgesia After Breast Cancer Surgery
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Surgery
Keywords: polyamines
pain
breast cancer
mastectomy
post operative pain
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
name: Insurance CNP foundation
First posted: 2006-03-20
Enrollment: 160
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: After surgery, sensitization and hyperexcitability of central nervous system result in acute and long lasting postoperative pain. It has been shown that N-methyl-D-aspartate (NMDA) receptors antagonist (such as ketamine) prevent this adverse neuroplasticity and potentiate analgesic drugs efficacy. Polyamines (putrescine, spermidine, spermine) are essential components of cells functioning and are also known as allosteric modulators of NMDA receptors. In animal studies, polyamine-free diet has confirmed these antinociceptive properties. This research aims at evaluating anti hyperalgesic properties of polyamine-free diet in women operated on breast cancer versus kétamine

Detailed description: This multicentric, single blind study will enrol 160 women (18-75 years old) operated on tumorectomy and adenectomy (T1, T2, T3, N0, N1, M0) for breast cancer. Patients will be randomly assigned in a 2x2 factorial plan : Group 1 = control (n = 40) ; group 2 = ketamine group administered during and 48 hours after a standardized anesthesia (n = 40) ; group 3 = polyamine-free diet, 1 week and 72 hours after surgery (n = 40) ; group 4 : ketamine + polyamine-free diet (n = 40).

The amount of morphine for the 24 first postoperative hours will be compared between each group as well as pain score, allodynia (Von Frey filaments) and hyperalgesia (algometer). Chronic pain occurrence (post-mastectomy pain syndrome) will be evaluated at 3 and 6 months using adequate questionnaire ( analgesic scale). Diet observance will be controlled preoperatively by a dosage of polyamines in circulating red cells blood.

Polyamines deprivation and ketamine ability to reduce postoperative pain will be compared (isobolographic method). Anti-hyperalgesic properties of ketamine have already been demonstrated in urologic, orthopaedic and abdominal surgery. In case of additive or synergistic effect of a polyamine deprivation such a strategic could be helpful to achieve better postoperative rehabilitation in reducing chronic pain after surgery.

Eligibility criteria: Inclusion Criteria:

* Breast cancer (T1, T2, T3, N0, N1, M0)
* Age : 18 - 75
* Asa 1-3
* left or right tumorectomy with complete lymphadenectomy
* left or right complete mastectomy with complete lymphadenectomy
* complete lymphadenectomy within one week following simple tumorectomy
* informed consent signed

Exclusion Criteria:

* inflammatory tumor requiring pre-operative radiotherapy
* previous history of total mastectomy or partial contralateral mastectomy
* chronic inflammatory disease treated by corticoids or NSAI
* chronic analgesic treatment
* anti-arrhythmic or anti-epileptic treatments
* morphinic treatment during the 7 days before surgery
* excessive alcohol consumption or addiction
* ketamine or neomycin contra-indication
* severe cardiovascular disease

Primary outcomes:
measure: Morphine requirement
timeFrame: for the 24 postoperative hours
Secondary outcomes:
measure: Pain intensity for the 4 days (and possibly at 7th day if the patient is still hospitalized) after surgery
timeFrame: 4 days
measure: Allodynia measurements
timeFrame: inclusion, 1, 2, 4 and 7 ddays after surgery
measure: Hyperesthesia measurements
timeFrame: inclusion, 1, 2, 4 and 7 ddays after surgery
measure: Chronic pain incidence
timeFrame: 3 and 6 months
measure: Late allodynia and/or hyperesthesia
timeFrame: 6 months
measure: safety of treatment
timeFrame: Along each patient folow-up
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CLCC-Institut Bergonie, service d'anesthésie réanimation, 229 cours de l'Argonne
city: Bordeaux
country: France
facility: département d'anesthésie-réanimation 3, hôpital Pellegrin
city: Nancy
country: France
facility: CLCC Alexis Vautrin
city: Paris
country: France
facility: APHParis Hôpital Pitié Salpétrière - Dépt. d'anesthésie réanimation
city: Saint Cloud
country: France
facility: CLCC Réné Huguenin de Saint Cloud
Study officials:
affiliation: DAR 3 -Pellegrin hospital-33076 Bordeaux - France
name: Pierre MAURETTE, Pr
role: PRINCIPAL_INVESTIGATOR
affiliation: University hospital - 33076 Bordeaux - France
name: Genevieve CHENE, Pr
role: STUDY_CHAIR
References: