Polyamine-free Diet to Prevent Post Surgery Hyperalgesia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Efficacy of a Polyamine-free Diet Associated or Not With Ketamine on Early and Late Hyperalgesia After Breast Cancer Surgery

Conditions
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Breast Cancer, Surgery

Intervention / Treatment
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* Behavioral: polyamine-free diet
* Drug: Ketamine or placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R+ / K+<br> | Behavioral: polyamine-free diet<br>* Polyamine-free diet in the 7 days befor surgery<br>Drug: Ketamine or placebo<br>* Peroperative and post operative (48h) ketamine injection<br>|
| Experimental: R+ / K-<br> | Behavioral: polyamine-free diet<br>* Polyamine-free diet in the 7 days befor surgery<br>Drug: Ketamine or placebo<br>* Peroperative and post operative (48h) ketamine injection<br>|
| Experimental: R- / K+<br> | Drug: Ketamine or placebo<br>* Peroperative and post operative (48h) ketamine injection<br>|
| Placebo Comparator: R- /K-<br> | Drug: Ketamine or placebo<br>* Peroperative and post operative (48h) ketamine injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Morphine requirement |  | for the 24 postoperative hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity for the 4 days (and possibly at 7th day if the patient is still hospitalized) after surgery |  | 4 days | 
| Allodynia measurements |  | inclusion, 1, 2, 4 and 7 ddays after surgery | 
| Hyperesthesia measurements |  | inclusion, 1, 2, 4 and 7 ddays after surgery | 
| Chronic pain incidence |  | 3 and 6 months | 
| Late allodynia and/or hyperesthesia |  | 6 months | 
| safety of treatment |  | Along each patient folow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polyamines, pain, breast cancer, mastectomy, post operative pain