Study to Evaluate the Efficacy of a Polyamine-deficient Diet for Treating Postoperative Pain After Abdominal Surgery (POLYAMAL)

A Prospective Randomized Multicenter Study to Evaluate the Efficacy of a Polyamine-deficient Diet for the Treatment of Postoperative Pain After Abdominal Surgery.

The aim of this study is to evaluate if a polyamine deficient diet started 7 days prior to a major abdominal surgery (eventration cure and digestive continuity) and followed 7 days post-surgery reduces the area under the curve of the numerical pain rating scale in the 72 hours post-surgery.

Study Overview

• Status: Recruiting
• Conditions: Digestive System Surgical Procedures
• Intervention / Treatment: Other: Polyamine Deficient Diet

Detailed Description

Morphine derivatives are known to be a major cause of postoperative ileus and also operative hyperalgesia. Operative hyperalgesia corresponds to an increase in morphine needs postoperatively which is proportional to the morphine dose necessary during the surgery. This effect is due to two mechanisms: opioids tolerance and induced hypersensitivity.

N-methyl-D-aspartate receptors (R-NMDA) play a key role in this induced hypersensitivity. Polyamines, organic compounds with several amines functions, are known R-NMDA agonists. They increase the phosphorylation of the tyrosine group within the NR2B subunit responsible for the inflammatory hyperalgesia.

Limiting the binding of polyamines to the R-NMDA seems an easy, safe and efficient way to limit the hypersensitivity induced post-operatively.

Most of the polyamines in the human body come from food. One study listed food regarding their polyamines content and allowed to check the safety of a polyamine deficient diet. Such a well-followed diet would allow to reduce by 20 the polyamines quantity present in the body.

The aim of this study is to evaluate whether a deficient polyamine diet introduced 7 days before and continued up to 7 days after an abdominal surgery requiring the use of morphine post-operatively reduces the post-operative pain, the consumption of analgesics (morphine) post-operatively and improve the recovery ability. Abdominals surgeries concerned will be the eventration cure and digestive continuity.

The medico-economic impact will be observed during this study.

• Study Type: Interventional
• Enrollment (Estimated): 278
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Claire Blanchard, MD-PhD; Phone Number: +33 (0)2 40 08 30 22; Email: claire.blanchard@chu-nantes.fr
• Study Contact Backup: Name: Laetitia Berly; Phone Number: +33 (0)2.53.52.62.04; Email: laetitia.berly@chu-nantes.fr

Study Locations

• France
  • Brest, France
    • Recruiting
    • CHRU Brest La Cavale Blanche
    • Contact: Jérémie Thereaux, MD PhD
  • Colombes, France, 92700
    • Not yet recruiting
    • Hôpital Louis Mourier from Ap-HP
    • Contact: David MOSZKOWICZ, Pr; Email: david.moszkowicz@aphp.fr
  • La Roche-sur-Yon, France
    • Recruiting
    • CHD Vendée
    • Contact: Emeric Abet
  • Nantes, France
    • Recruiting
    • CHU Nantes Hôtel Dieu
    • Contact: Blanchard Claire, MD PhD
    • Sub-Investigator: Tristan Greilsamer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult (>18 years)
• Indication for a " major " abdominal surgery as second surgical procedure : cure of eventration and restoration of digestive continuity
• Intended Use of a Patient Controlled Morphine Pump (PCA) postoperatively or taking oral opioids
• Possible follow-up during 7 months (post-operative consultation at 1 month and 6 months only if postoperative pain or complications)
• Written informed consent form obtained from the patient
• Affiliated to the social security

Exclusion Criteria:

• Pregnant women
• Minor, adult under guardianship or benefiting from a legal protection
• Oncological surgery
• Surgery not painful (cholecystectomy, hernia, thyroidectomy, bariatric surgery)
• Drug addicts patients, or under opiate dependency
• Chronic pain patients (pain over 3 months)
• Patients in nursing home or convalescence home (diet non possible in institution)
• Planned hospitalisation before the intervention (during the 7 days before the surgery)
• Severe undernutrition defined by the HAS criteria (weight loss > 10% in 1 month and/or > 15% in 6 months, albumin at inclusion <15g/l)
• Patient refusing the possibility to change his eating habits
• Oral feeding impossible preoperatively
• Patient not able to express himself on their pain (silent, …)
• Decompensated psychiatric pathologies (severe depression syndrome,…)
• Patient unable to understand the protocol and/or to give his informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Polyamine deficient diet; Diet low in polyamines: the estimated calculated dose is 20 times lower that in an usual diet	Other: Polyamine Deficient Diet; Diet low in polyamines: the estimated calculated dose is 20 times lower that in an usual diet
No Intervention: Control; Usual Diet plus two snacks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To show a 20% decrease of the area under the curve for the numerical pain rating scale in the 72 hours post-operative in the polyamine deficient diet group	To show a 20% decrease of the area under the curve for the numerical pain rating scale in the 72 hours post-operative in the polyamine deficient diet group measured every 6 hours in resting position, upon return from the operative room	72 hours post-surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the analgesics consumption post-operatively	Measure of the analgesics consumption by the nurse during hospitalisation and by the patient with the patient book up to 15 days postsurgery	15 days post-surgery
Change in the main dimension of pain	Evaluation of the main dimension of pain using the Brief Pain Inventory (BPI)	6 months post-surgery
Change of the recovery time of the gas transit	Evaluation of the time to recover the gas transit post-surgery (in days)	6 months post-surgery
Change of duration of urinary catheterization	Recovery of spontaneous urination post-surgery (in days)	6 months post-surgery
Change in the delay before the first postoperative lift	Time before walking post-surgery (in days)	6 months post-surgery
Change in length of hospitalisation stay and sick leave	Hospitalisation time and sick leave (in days)	6 months post-surgery
Change in neuropathic pain: Neuropathic pain scale (DN4)	Use of the Neuropathic pain scale for patients seen for their postsurgery pain or complications. The scale contains 10 questions, the range is between 0-10, 10 being the worst score.	6 months post-surgery
Change in global health status	Use of autoquestionnaire EuroQol-5 Dimension (EQ-5D) to evaluate the global health status of the patients. The scale contains two parts, the first one contains 5 items to be completed by the patients with 5 levels for each item, the worst score being 55555. The second part is an analog visual scale with a range between 0-100, 0 being the worst score.	1 month before surgery, 1 month and 6 months post-surgery
Change of the recovery ability	Evaluation of the recovery ability using the Quality of Recovery-15 Questionnaire (QoR-15)	1 month before surgery, 1 month and 6 months post-surgery
Change in the quality of life	Assessment of the patient's quality of life by using the Short-Form Health Survey 36 questionnaire (SF-36)	1 month before surgery, 1 month and 6 months post-surgery

Collaborators and Investigators

• Sponsor: Nantes University Hospital
• Collaborators: Centre de Recherche en Nutrition Humaine Ouest (CRNH)
• Investigators: Principal Investigator: Claire Blanchard, MD-PhD, CHU Nantes

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2020
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: January 3, 2020
• First Submitted That Met QC Criteria: January 6, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): May 30, 2023
• Last Update Submitted That Met QC Criteria: May 26, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Hypersensitivity; Morphine; Postoperative pain; Abdominal surgery; Polyamine
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative
• Other Study ID Numbers: RC19_0023

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No