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Paracetamol and Neuropathic Pain (PAeoNy)

Primary Purpose

Neuropathic Pain

Status

Terminated

Phase

Phase 2

Locations

France

Study Type

Interventional

Intervention

paracetamol

Placebo comparator

About this trial

This is an interventional treatment trial for Neuropathic Pain focused on measuring Paracetamol, Neuropathic pain, Analgesic effect, Pharmacogenetics, Biological parameters, Cognitivo-emotional parameters

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient aged 18 to 65 years,
Patient suffering from chronic pain (for more than 3 months) with the characteristics of peripheral neuropathy and having pain assessed by a numerical scale ≥ 3 for one week, with at least 10 assessments completed,
Patient agrees with not to take paracetamol, other than the treatment provided as part of the protocol, from inclusion to completion of the study,
Acceptance to give a written consent.

Exclusion Criteria:

Patient taking paracetamol daily,
Patient with a contraindication to paracetamol administration (liver or renal failure, ...),
Patient with a biological evaluation evaluated by the investigator as not compatible with the trial,
Patient with a medical and/or surgical history evaluated by the investigator to be not compatible with the trial,
Patient with drug treatments evaluated by the investigator to be not compatible with the trial,
Pregnant or nursing woman,
Patient with a cooperation and an understanding that does not allow for a strict compliance under the conditions set out in the protocol,
Patient participating in another clinical trial, or being in an exclusion period, or having received a total amount of compensation exceeding 4500 euros over the 12 months preceding the start of the trial,
Patient benefiting from a legal protection measure (curatorship, guardianship, protection of justice...),
Patient not affiliated to the French Social Security system,
Paracetamol intake during wash-out period.

Sites / Locations

Lise LACLAUTRE

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

Paracetamol and placebo comparator (Group 1)

Paracetamol and placebo comparator (Group 2)

Arm Description

Neuropathic pain patients taking either paracetamol or placebo according to the randomization plan

Neuropathic pain patients taking either paracetamol (if during period 1 they received placebo) or placebo (if during period 1 they received paracetamol)

Outcomes

Primary Outcome Measures

Pain intensity change between period 1 and 2

Pain intensity change between period 1 and 2, measured by numerical pain rating scale (NPRS) over one week (two evaluations per day, morning and evening) following the taking of paracetamol/ placebo.

Secondary Outcome Measures

Treatment responders at 30% (NPRS)

Calculation of the decrease of NPRS by at least 30% between the beginning and the end of the treatment period (at least 30% difference between the average of four NPRS measurements over 2 days before the start of the treatment period and the average of the four NPRS measurements over 2 days at the end of the treatment period). The number of paracetamol responders will be compared to the number of placebo responders.

Treatment responders at 50% (NPRS)

Calculation of the decrease of NPRS by at least 50% between the beginning and the end of the treatment period (at least 50% difference between the average of four NPRS measurements over 2 days before the start of the treatment period and the average of four NPRS measurements over 2 days at the end of the treatment period). The number of paracetamol responders will be compared to the number of placebo responders.

Number of paroxysms

The number of paroxysms will be listed by the patient in the daily pain diary during all the study (28 days).

Paroxysms intensity (NPRS)

The average pain of paroxyms will be evaluated by the patient in the daily pain diary during all the study (28 days). The pain intensity will be measured by NPRS: the scale ranges from 0 no pain to 10 maximal tolerable pain

Assessment of paracetamol (and placebo) consumption

The number of paracetamol (and placebo) capsules intake will be listed by the patient in the pain diary during the 4 weeks of the study.

Assessment of dynamic mechanical allodynia

Dynamic mechanical allodynia (DMA) will be evaluated by a standardized fine filament brush (Somedic, ~200-400mN) which will be moved laterally, slowly and without support, with a movement back and forth over an area of skin. Patients will be seated comfortably in a quiet room. This light touch will be applied 5 times. The sensation perceived by the patient, during each stimulus, will be rated using an ENV (0 - 10), where a score of 0 equals "no pain" and a score of 10 equals "pain maximum imaginable". The DMA will be quantified as the geometric mean of all scores corresponding to each stimulation

Assessment of liver and renal functions

A tube will be taken for biochemistry analysis of alanine amino transferase, aspartate aminotransferase and bilirubin to assess the liver function and creatine level to assess the renal function at each visit. The assays will be carried out by the medical biochemistry laboratory of Clermont-Ferrand University Hospital.

Blood dosage of glutathione

In order to measure the plasma glutathione level, a blood sample will be taken at each visit. After centrifugation, an aliquot will be performed to recover the plasma. The tubes will be frozen at -80°C for subsequent dosage.

Blood dosage of paracetamol and its metabolites

In order to determine the plasma concentration of paracetamol and its metabolites, four blood samples will be taken at D1, D8, D15 and D22. After centrifugation, an aliquot will be performed to recover the plasma. The tubes will be frozen at -80°C for subsequent dosage.

Urinary dosage of paracetamol and its metabolites

In order to determine the urinary concentration of paracetamol and its metabolites, four urine samples will be taken before and after each study period at D1, D7, D15 and D21 and will be frozen at -20°C for subsequent dosage.

Analysis of pharmacogenetics parameters

Pharmacogenetics screening will focus on the metabolism of paracetamol and more specifically on the detection of the presence of one or more variant(s) of the genes UGT2B15, SULT1A1 and TRPV1. This screening will be performed on a single blood sample on D-6 (first visit). Two tubes will be taken and placed directly in the freezer at -80°C. This biological collection will be kept until the analysis.

Impact of paracetamol on patient feeling and satisfaction by Global Patient Impression of Change (PGIC)

This scale is used to assess patient satisfaction with treatment by choosing an answer among 8 responses (ranging from "very strongly enhanced" to "very strongly improved") to reflect their overall health.

Impact of paracetamol on cognitive parameters evaluated by Cantab® tests: Motor Screening Test (MOT), Stocking of Cambridge (SOC), Information Sampling task (IST).

The Cantab® test is a validated tool for exploring cognitive functions. It consists of a choice of tests that explore several cognitive dimensions: Planning (IST), Decision-making (SOC). The tests are done on a computer screen with a record of the score obtained for each test. The scores of the different tests are added and the total score compared between the 2 groups. Patients will be required to complete these tests once during their visits.

Emotional status by Hospital Anxiety and Depression scale (HAD)

The Hospital Anxiety and Depression scale is a self-administered questionnaire in 14 items completed by the patient. It is used to determine the levels of anxiety and depression. Seven of the items relate to anxiety and seven relate to depression. Global score ranges from 0 to 42.

Sleep by the Pittsburgh Sleep Quality Index (PSQI)

This questionnaire consists of 19 items and is used to measure sleep quality. It consists of 7 domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication and daytime dysfunction.

Descriptive analysis of adverse event of paracetamol use.

The adverse event will be reported by the patient on his pain diary during all the study. Furthermore, a daily phone-call will be performed by the team project during the two period of treatment

Full Information

NCT ID

NCT03559985

First Posted

May 11, 2018

Last Updated

October 6, 2022

Sponsor

University Hospital, Clermont-Ferrand

1. Study Identification

Unique Protocol Identification Number

NCT03559985

Brief Title

Paracetamol and Neuropathic Pain

Acronym

PAeoNy

Official Title

Analgesic Effect of Paracetamol in Neuropathic Pain Patients

Study Type

Interventional

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Terminated

Why Stopped

Recruitment difficulties

Study Start Date

August 20, 2018 (Actual)

Primary Completion Date

October 8, 2020 (Actual)

Study Completion Date

August 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Hospital, Clermont-Ferrand

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

Brief Summary

The aim of this study is to evaluate the analgesic effect of paracetamol in patients suffering from pain with a peripheral neuropathic component in the presence of their usual treatment.

Detailed Description

This is an interventional, randomized, placebo-controlled, double-blind, crossover study about the use of paracetamol in therapeutic doses in peripheral neuropathic pain patients. The analgesic effect of paracetamol will be assessed by the painful intensity measured by numerical pain rating scale over one week after taking paracetamol/placebo. The secondary objectives will be: To determine the number of patients in whom paracetamol is effective in reducing pain by at least 30% and 50%, To evaluate the effect of paracetamol on pain, on the number and intensity of paroxysms, To evaluate paracetamol consumption, To evaluate the effect of paracetamol on neuropathic pain patient, To evaluate the effect of paracetamol on mechanical allodynia, To monitor routine biological parameters (liver function), Compare Glutathione (GSH) concentrations before and after taking paracetamol, To perform a blood test for paracetamol and its metabolites before and after each study period, To perform urine dosage of paracetamol and its metabolites before and after each study period, To study pharmacogenetics parameters, To evaluate patient feeling and satisfaction after taking paracetamol, To evaluate the effect of paracetamol on cognition, anxiety, depression and sleep by different questionnaires, To collect adverse events.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuropathic Pain

Keywords

Paracetamol, Neuropathic pain, Analgesic effect, Pharmacogenetics, Biological parameters, Cognitivo-emotional parameters

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Crossover Assignment

Model Description

After a week of pre-selection (D-6 to D0), each patient will receive successively in random order each of the 2 products (paracetamol and placebo) with one wash-out period of 7 days between each administration.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Paracetamol 500 mg capsules (Doliprane® 500 mg) will remain packaged in their blister packs of origin. The necessary quantity of capsules will be packaged in a box labelled at the corresponding period (period 1 or 2). Lactose capsules (placebo) of the same size and colour as the Paracetamol capsules (Doliprane® 500 mg) will be bought by the CHU Pharmacy from Clermont-Ferrand. The capsules will then be blistered; the necessary quantity of capsules placebo will be packaged in the same box used for paracetamol, labelled at the time of the treatment (period 1 or 2).

Allocation

Randomized

Enrollment

43 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Paracetamol and placebo comparator (Group 1)

Arm Type

Other

Arm Description

Neuropathic pain patients taking either paracetamol or placebo according to the randomization plan

Arm Title

Paracetamol and placebo comparator (Group 2)

Arm Type

Other

Arm Description

Neuropathic pain patients taking either paracetamol (if during period 1 they received placebo) or placebo (if during period 1 they received paracetamol)

Intervention Type

Drug

Intervention Name(s)

paracetamol

Intervention Description

Period 1 (D1 to D7): 500 mg (paracetamol or placebo) to be repeated if necessary, depending on the intensity of pain, after 4 hours minimum between each treatment intake, with a maximum dose of 3 g/day, corresponding to 6 capsules per day. Wash-out period (D8 to D14): patients should not take paracetamol during this week. Period 2 (D15 to D21): 500 mg per dose (paracetamol or placebo) to be repeated if necessary, depending on the intensity of pain, after 4 hours minimum between each treatment intake, with a maximum dose of 3 g/day, corresponding to 6 capsules per day.

Intervention Type

Other

Intervention Name(s)

Placebo comparator

Intervention Description

Primary Outcome Measure Information:

Title

Pain intensity change between period 1 and 2

Description

Pain intensity change between period 1 and 2, measured by numerical pain rating scale (NPRS) over one week (two evaluations per day, morning and evening) following the taking of paracetamol/ placebo.

Time Frame

Day 1 to Day 7 (one week) and Day 15 to Day 21 (one week).

Secondary Outcome Measure Information:

Title

Treatment responders at 30% (NPRS)

Description

Time Frame

During 2 days before period 1 (mean of Day -1 and Day 0) and at the end of period 1 (mean of Day 6 and Day 7); during 2 days before period 2 (mean of Day 13 and Day 14) and at the end of period 2 (mean of Day 20 and Day 21).

Title

Treatment responders at 50% (NPRS)

Description

Time Frame

Title

Number of paroxysms

Description

The number of paroxysms will be listed by the patient in the daily pain diary during all the study (28 days).

Time Frame

Before period 1 (Day -6 to Day 0), over a week during period 1 (Day 1 to Day 7), over a week during wash-out (Day 8 to Day 14) and over a week during period 2 (Day 15 to Day 21).

Title

Paroxysms intensity (NPRS)

Description

Time Frame

(Day -6 to Day 0), over a week during period 1 (Day 1 to Day 7), over a week during wash-out (Day 8 to Day 14) and over a week during period 2 (Day 15 to Day 21).

Title

Assessment of paracetamol (and placebo) consumption

Description

The number of paracetamol (and placebo) capsules intake will be listed by the patient in the pain diary during the 4 weeks of the study.

Time Frame

At Day1, Day8, Day15, Day22

Title

Assessment of dynamic mechanical allodynia

Description

Time Frame

At Day1, Day8, Day15, Day22

Title

Assessment of liver and renal functions

Description

Time Frame

At Day-6, Day1, Day8, Day15, Day22

Title

Blood dosage of glutathione

Description

Time Frame

At Day-6, Day1, Day8, Day15, Day22

Title

Blood dosage of paracetamol and its metabolites

Description

Time Frame

At Day1, Day8, Day15, Day22

Title

Urinary dosage of paracetamol and its metabolites

Description

Time Frame

At Day1, Day7, Day15, Day21

Title

Analysis of pharmacogenetics parameters

Description

Time Frame

At the pre-selection visit (Day-6).

Title

Impact of paracetamol on patient feeling and satisfaction by Global Patient Impression of Change (PGIC)

Description

Time Frame

At Day1, Day8, Day15, Day22

Title

Impact of paracetamol on cognitive parameters evaluated by Cantab® tests: Motor Screening Test (MOT), Stocking of Cambridge (SOC), Information Sampling task (IST).

Description

Time Frame

At Day1, Day8, Day15, Day22

Title

Emotional status by Hospital Anxiety and Depression scale (HAD)

Description

Time Frame

At Day1, Day8, Day15, Day22

Title

Sleep by the Pittsburgh Sleep Quality Index (PSQI)

Description

Time Frame

At Day1, Day8, Day15, Day22

Title

Descriptive analysis of adverse event of paracetamol use.

Description

The adverse event will be reported by the patient on his pain diary during all the study. Furthermore, a daily phone-call will be performed by the team project during the two period of treatment

Time Frame

Pain diary: over 4 weeks: At the pre-selection visit (Day -6) to the end of the study (Day 22).

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient aged 18 to 65 years, Patient suffering from chronic pain (for more than 3 months) with the characteristics of peripheral neuropathy and having pain assessed by a numerical scale ≥ 3 for one week, with at least 10 assessments completed, Patient agrees with not to take paracetamol, other than the treatment provided as part of the protocol, from inclusion to completion of the study, Acceptance to give a written consent. Exclusion Criteria: Patient taking paracetamol daily, Patient with a contraindication to paracetamol administration (liver or renal failure, ...), Patient with a biological evaluation evaluated by the investigator as not compatible with the trial, Patient with a medical and/or surgical history evaluated by the investigator to be not compatible with the trial, Patient with drug treatments evaluated by the investigator to be not compatible with the trial, Pregnant or nursing woman, Patient with a cooperation and an understanding that does not allow for a strict compliance under the conditions set out in the protocol, Patient participating in another clinical trial, or being in an exclusion period, or having received a total amount of compensation exceeding 4500 euros over the 12 months preceding the start of the trial, Patient benefiting from a legal protection measure (curatorship, guardianship, protection of justice...), Patient not affiliated to the French Social Security system, Paracetamol intake during wash-out period.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Gisèle PICKERING

Organizational Affiliation

University Hospital, Clermont-Ferrand

Official's Role

Principal Investigator

Facility Information:

Facility Name

Lise LACLAUTRE

City

Clermont-Ferrand

ZIP/Postal Code

63003

Country

France

12. IPD Sharing Statement

Learn more about this trial

Paracetamol and Neuropathic Pain

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