Polyamine-free Diet to Prevent Post Surgery Hyperalgesia (PoLyDOL)

University Hospital of Bordeaux

Status and phase: Completed; Phase 2

Conditions: Breast Cancer; Surgery

Treatments: Behavioral: polyamine-free diet; Drug: Ketamine or placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT00304850

2002-004

9258-03

Details and patient eligibility

About

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

Full 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.

Enrollment: 160 estimated patients

Sex: Female

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

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160 participants in 4 patient groups, including a placebo group

R+ / K+

Experimental group

Treatment:

Behavioral: polyamine-free diet

Drug: Ketamine or placebo

R+ / K-

Experimental group

Treatment:

Behavioral: polyamine-free diet

Drug: Ketamine or placebo

R- / K+

Experimental group

Treatment:

Drug: Ketamine or placebo

R- /K-

Placebo Comparator group

Treatment:

Drug: Ketamine or placebo