Back to resultsMemantine and Post-mastectomy Neuropathic Pain (CLEMANTINE)
Primary Purpose
Neuropathic Pain
Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Memantine
no memantine
Sponsored by
About this trial
This is an interventional treatment trial for Neuropathic Pain focused on measuring Memantine, post-mastectomy, prophylaxis, Neuropathic pain, Cognitive-emotional parameters
Eligibility Criteria
Inclusion Criteria:
- Patient ≥18 years,
- Patient with a diagnosis of breast cancer, programmed for mastectomy with or without axillary dissection and neoadjuvant chemotherapy,
- Patient able to understand and willing to follow the study protocol,
- Acceptance to give a written consent.
Exclusion Criteria:
- Patient with a contraindication to memantine administration (hypertension, severe cardiac or hepatic insufficiency, stroke),
- Patient with diabetes (type I and II),
- Patient with renal insufficiency,
- Patient with drug treatments evaluated by the investigator to be not compatible with the trial,
- Patient treated with specific drugs (amantadine, ketamine, dextromethorphan, L-Dopa, dopaminergic, anticholinergic agonists, barbituric, neuroleptic, IMAO, antispastic agents, dantrolen or baclofen, phenytoin, cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine, hydrochlorothiazide, warfarine),
- Patient with alcohol addiction,
- Epileptic patient or history of epileptic seizure or convulsions,
- 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...),
Sites / Locations
- Chu Clermont-Ferrand
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Memantine group
Usual care group
Arm Description
Memantine will be given orally for four weeks starting two weeks before surgery. Memantine will be given in increasing doses: 5 mg/day for 3 days; 10 mg/day for 3 days; 15 mg/day for 3 days and 20 mg/day for 5 days.
Concerning the comparator group, patients will be followed in the same way as those in the "memantine" group except that they will not receive the study treatment.
Outcomes
Primary Outcome Measures
Numerical pain rating scale (NPRS)
The primary endpoint is the measure of the average pain intensity assessed over the 5 days prior to the 3-month post-surgery visit by NPRS, in the "memantine" and "usual care" groups. This scale ranges from 0 no pain to 10 maximal tolerable pain.
Secondary Outcome Measures
Analgesic consumption
Post-operative evaluation of analgesic consumption during 12 months, particularly morphine consumption with a daily pain diary and weekly phone call.
Neuropathic pain characteristics
Neuropathic Pain in 4 questions" (DN4): DN4 is a clinical tool for the diagnosis of neuropathic pain. This questionnaire has four questions divided into 10 items related to the interview (ie, symptoms) and to the sensory examination (ie, signs). The investigator asks and examines the patient and notes a response "no" or "yes" for each item: "yes" is scored as "1" and "no" is scored as "0". The sum of scores gives the total score of the patient (/10). DN4 is considered as positive if the patient obtains a score of 4/10.
Neuropathic pain evaluation by Neuropathic pain symptom Inventory (NPSI) questionnaire.
NPSI is a self-questionnaire and includes 10 pain descriptors. Intensity is rated on 0 to 10 numerical scales and two temporal items are designed to assess spontaneous ongoing pain duration and the number of pain paroxysms over 24 hours. This questionnaire discriminates five distinct clinically relevant dimensions: spontaneous burning pain, spontaneous deep pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia. Each item is calculated on 10 and the overall test score is scored on 100.
Pain evaluation by the Brief Pain Inventory (BPI).
Brief Pain Inventory is a self-administered questionnaire with seven items that measured how much pain interfered with various daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep
Pain evaluation by the McGill Pain questionnaire
This questionnaire allows to describe pain experienced during the last 48 hours. It has fifty eight qualifiers divided into sixteen items (A to P). Each qualifier is rated from 0 to 4, where 0 = absent, 1 = low, 2 = moderate, 3 = strong, 4 = very strong. The score is divided between two subclasses, sensory subclass (items A to I) and emotional subclass (items J to P).
Assessment of cognitive parameters by the trail making test (TMT).
This non-verbal cognitive test assesses the ability of speed, executive functions, attention, concentration, visual perceptual speed. The test takes place in two parts. In Part A, circles are numbered from 1 to 25 and the patient must connect with lines the numbers in ascending order (1-2-3-4, etc.). In Part B, the circles contain numbers from 1 to 13 and letters from A to L, the patient must connect the circles with lines but alternating numbers and letters (1A-2B -3C, etc.). The patient must connect the circles as quickly as possible for both parts of the test, without lifting the pen from the paper. The TMT B additionally provides an estimate of mental flexibility.
Assessment of cognitive parameters by the Digit symbol substitution test (DSST).
DSST is a neuropsychological, nonverbal test, which assesses cognitive deficit and brain damage associated with aging and/or depression. It also evaluates learning ability, concentration and attention. It consists in combining pairs of symbols and numbers as quickly as possible and the score is the correct number of symbols in the time allowed (e.g. 90 or 120 seconds).
Assessment of cognitive parameters with the Functional Assessment of Cancer Therapy Cognitive Function (FACT-COG).
The items are rated using a 5-point Likert scale ranged 0 from 4. This questionnaire is composed by four subscales: 2 subscales ranged as following: 0 (never), 1 (one time a week), 2 (two to three times a week), 3 (every day) and 4 (several times a day): Perceived cognitive impairments subscale and comments from others subscale and two others subscale ranged as following: 0 (not at all), 1 (a little), 2 (moderately), 3 (much) and 4 (enormously): Perceived cognitive abilities and impact of quality of life subscales. The total score is obtained with the sum of these 4 subscales
Quality of life assessment by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30).
The average of some questions lead to the score of 15 subscales reported on 100: 9 subscales consisting of several items: 5 subscales measuring functional status (physical, role, social, emotional, cognitive), three subscales measuring symptoms (fatigue, pain, nausea and vomiting) and a global subscale of quality of life and health. Finally, six items/isolated symptoms, covering cancer symptoms and frequent side effects of cancer therapies (e.g. loss of appetite) are also included in the questionnaire. For the 6 item assessing the isolated symptoms and some subscales assessing functional status (as physical, role, social cognitive, emotional) and subscales measuring symptoms (fatigue, pain nausea and vomiting): higher values represent a worse outcome. Concerning subscale of quality of life and health, higher values represent a better outcome.
Anxiety and depression assessment with the Hospital Anxiety and Depression scale (HAD).
The anxiety sub-score is obtained by summing items relate to anxiety (Subscore Anxiety (A): /21). The depression sub-score is obtained by summing items relate to depression (subscore Depression: /21). For each of the two subscores, if a subject obtain a score ranged from: 0 to 7, he is considered as "normal"; 8-10 = Borderline abnormal (borderline case) and 11-21 = Abnormal (case).
Sleep assessment with the Pittsburgh Sleep Quality Index (PSQI)
The 19 self-rated items are combined to form seven "component" scores, each of which has a range of 0-3 points (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication and daytime dysfunction).In all cases, a score of "0" indicates no difficulty, while a score of "3" indicates severe difficulty. The seven component scores are then added to yield one "global" score, with a range of 0-21 points, "0" indicating no difficulty and "21" indicating severe difficulties in all areas
Full Information
NCT ID
NCT03686774
First Posted
September 18, 2018
Last Updated
February 1, 2019
Sponsor
University Hospital, Clermont-Ferrand
1. Study Identification
Unique Protocol Identification Number
NCT03686774
Brief Title
Memantine and Post-mastectomy Neuropathic Pain
Acronym
CLEMANTINE
Official Title
Effect of Oral Administration of Memantine in Pre and Post-surgery in the Prevention of Post-mastectomy Neuropathic Pain
Study Type
Interventional
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Unknown status
Study Start Date
February 15, 2019 (Anticipated)
Primary Completion Date
January 31, 2022 (Anticipated)
Study Completion Date
January 31, 2022 (Anticipated)
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
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The aim of this study is to evaluate if memantine administered for four weeks starting two weeks before surgery induces a decrease in pain intensity at 3 months post-mastectomy.
Detailed Description
This is a randomized, controlled, open-label study in patients undergoing mastectomy. Patients included in this trial will receive memantine or not. For patients in the "memantine" group, the treatment will be given in titration (maximum dose of 20 mg/day). Concerning the comparator group, patients will be followed in the same way as those in the "memantine" group except that they will not receive the study treatment. Whether it is the "memantine" group or the "usual care" group, visits will be scheduled under the usual following conditions of the participating center.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuropathic Pain
Keywords
Memantine, post-mastectomy, prophylaxis, Neuropathic pain, Cognitive-emotional parameters
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Masking Description
no masking
Allocation
Randomized
Enrollment
150 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Memantine group
Arm Type
Experimental
Arm Description
Memantine will be given orally for four weeks starting two weeks before surgery. Memantine will be given in increasing doses: 5 mg/day for 3 days; 10 mg/day for 3 days; 15 mg/day for 3 days and 20 mg/day for 5 days.
Arm Title
Usual care group
Arm Type
Other
Arm Description
Concerning the comparator group, patients will be followed in the same way as those in the "memantine" group except that they will not receive the study treatment.
Intervention Type
Drug
Intervention Name(s)
Memantine
Intervention Description
Women provide written informed consent prior to their participation in the study, during their Anesthesiology visit. After baseline assessments (15 days before surgery: Day 0 - 15) of pain intensity, cognitive, quality of life and quality of sleep questionnaires, participants will be randomized in two parallel groups: "memantine" (n=75) or "usual care" (n=75). Memantine will be given orally for four weeks starting two weeks before surgery. Endpoints will be assessed 15 days (Day 0 + 15), 3 months (Day 0 + 3 months), 6 months (Day 0 + 6 months) et 12 months (Day 0 + 12 months) post-mastectomy. In order to maintain a good compliance and to verify that women do not develop adverse events, patients will be called once a week by phone. A booklet for monitoring will be completed daily by the patient for 3 months from the day of surgery.
Intervention Type
Other
Intervention Name(s)
no memantine
Intervention Description
Concerning the comparator group, patients will be followed in the same way as those in the "memantine" group except that they will not receive the study treatment
Primary Outcome Measure Information:
Title
Numerical pain rating scale (NPRS)
Description
The primary endpoint is the measure of the average pain intensity assessed over the 5 days prior to the 3-month post-surgery visit by NPRS, in the "memantine" and "usual care" groups. This scale ranges from 0 no pain to 10 maximal tolerable pain.
Time Frame
over the 5 days prior to the 3-month post-surgery visit
Secondary Outcome Measure Information:
Title
Analgesic consumption
Description
Post-operative evaluation of analgesic consumption during 12 months, particularly morphine consumption with a daily pain diary and weekly phone call.
Time Frame
Over 12 months
Title
Neuropathic pain characteristics
Description
Neuropathic Pain in 4 questions" (DN4): DN4 is a clinical tool for the diagnosis of neuropathic pain. This questionnaire has four questions divided into 10 items related to the interview (ie, symptoms) and to the sensory examination (ie, signs). The investigator asks and examines the patient and notes a response "no" or "yes" for each item: "yes" is scored as "1" and "no" is scored as "0". The sum of scores gives the total score of the patient (/10). DN4 is considered as positive if the patient obtains a score of 4/10.
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
Title
Neuropathic pain evaluation by Neuropathic pain symptom Inventory (NPSI) questionnaire.
Description
NPSI is a self-questionnaire and includes 10 pain descriptors. Intensity is rated on 0 to 10 numerical scales and two temporal items are designed to assess spontaneous ongoing pain duration and the number of pain paroxysms over 24 hours. This questionnaire discriminates five distinct clinically relevant dimensions: spontaneous burning pain, spontaneous deep pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia. Each item is calculated on 10 and the overall test score is scored on 100.
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
Title
Pain evaluation by the Brief Pain Inventory (BPI).
Description
Brief Pain Inventory is a self-administered questionnaire with seven items that measured how much pain interfered with various daily activities, including general activity, walking, work, mood, enjoyment of life, relations with others, and sleep
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
Title
Pain evaluation by the McGill Pain questionnaire
Description
This questionnaire allows to describe pain experienced during the last 48 hours. It has fifty eight qualifiers divided into sixteen items (A to P). Each qualifier is rated from 0 to 4, where 0 = absent, 1 = low, 2 = moderate, 3 = strong, 4 = very strong. The score is divided between two subclasses, sensory subclass (items A to I) and emotional subclass (items J to P).
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
Title
Assessment of cognitive parameters by the trail making test (TMT).
Description
This non-verbal cognitive test assesses the ability of speed, executive functions, attention, concentration, visual perceptual speed. The test takes place in two parts. In Part A, circles are numbered from 1 to 25 and the patient must connect with lines the numbers in ascending order (1-2-3-4, etc.). In Part B, the circles contain numbers from 1 to 13 and letters from A to L, the patient must connect the circles with lines but alternating numbers and letters (1A-2B -3C, etc.). The patient must connect the circles as quickly as possible for both parts of the test, without lifting the pen from the paper. The TMT B additionally provides an estimate of mental flexibility.
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
Title
Assessment of cognitive parameters by the Digit symbol substitution test (DSST).
Description
DSST is a neuropsychological, nonverbal test, which assesses cognitive deficit and brain damage associated with aging and/or depression. It also evaluates learning ability, concentration and attention. It consists in combining pairs of symbols and numbers as quickly as possible and the score is the correct number of symbols in the time allowed (e.g. 90 or 120 seconds).
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
Title
Assessment of cognitive parameters with the Functional Assessment of Cancer Therapy Cognitive Function (FACT-COG).
Description
The items are rated using a 5-point Likert scale ranged 0 from 4. This questionnaire is composed by four subscales: 2 subscales ranged as following: 0 (never), 1 (one time a week), 2 (two to three times a week), 3 (every day) and 4 (several times a day): Perceived cognitive impairments subscale and comments from others subscale and two others subscale ranged as following: 0 (not at all), 1 (a little), 2 (moderately), 3 (much) and 4 (enormously): Perceived cognitive abilities and impact of quality of life subscales. The total score is obtained with the sum of these 4 subscales
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
Title
Quality of life assessment by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30).
Description
The average of some questions lead to the score of 15 subscales reported on 100: 9 subscales consisting of several items: 5 subscales measuring functional status (physical, role, social, emotional, cognitive), three subscales measuring symptoms (fatigue, pain, nausea and vomiting) and a global subscale of quality of life and health. Finally, six items/isolated symptoms, covering cancer symptoms and frequent side effects of cancer therapies (e.g. loss of appetite) are also included in the questionnaire. For the 6 item assessing the isolated symptoms and some subscales assessing functional status (as physical, role, social cognitive, emotional) and subscales measuring symptoms (fatigue, pain nausea and vomiting): higher values represent a worse outcome. Concerning subscale of quality of life and health, higher values represent a better outcome.
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
Title
Anxiety and depression assessment with the Hospital Anxiety and Depression scale (HAD).
Description
The anxiety sub-score is obtained by summing items relate to anxiety (Subscore Anxiety (A): /21). The depression sub-score is obtained by summing items relate to depression (subscore Depression: /21). For each of the two subscores, if a subject obtain a score ranged from: 0 to 7, he is considered as "normal"; 8-10 = Borderline abnormal (borderline case) and 11-21 = Abnormal (case).
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
Title
Sleep assessment with the Pittsburgh Sleep Quality Index (PSQI)
Description
The 19 self-rated items are combined to form seven "component" scores, each of which has a range of 0-3 points (subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleep medication and daytime dysfunction).In all cases, a score of "0" indicates no difficulty, while a score of "3" indicates severe difficulty. The seven component scores are then added to yield one "global" score, with a range of 0-21 points, "0" indicating no difficulty and "21" indicating severe difficulties in all areas
Time Frame
At baseline (15 days before surgery: Day 0 - 15 days), visit 3 (Day 0 + 16 days), visit 4 (Day 0 + 3 months), visit 5 (Day 0 + 6 months) and visit 6 (Day 0 + 12 months).
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patient ≥18 years,
Patient with a diagnosis of breast cancer, programmed for mastectomy with or without axillary dissection and neoadjuvant chemotherapy,
Patient able to understand and willing to follow the study protocol,
Acceptance to give a written consent.
Exclusion Criteria:
Patient with a contraindication to memantine administration (hypertension, severe cardiac or hepatic insufficiency, stroke),
Patient with diabetes (type I and II),
Patient with renal insufficiency,
Patient with drug treatments evaluated by the investigator to be not compatible with the trial,
Patient treated with specific drugs (amantadine, ketamine, dextromethorphan, L-Dopa, dopaminergic, anticholinergic agonists, barbituric, neuroleptic, IMAO, antispastic agents, dantrolen or baclofen, phenytoin, cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine, hydrochlorothiazide, warfarine),
Patient with alcohol addiction,
Epileptic patient or history of epileptic seizure or convulsions,
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...),
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lise LACLAUTRE
Phone
04 73 75 49 63
Email
drci@chu-clermontferrand.fr
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
Chu Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lise LACLAUTRE
Phone
04 73 75 49 63
Email
drci@chu-clermontferrand.fr
First Name & Middle Initial & Last Name & Degree
Gisèle PICKERING
First Name & Middle Initial & Last Name & Degree
Dominique JOLY
First Name & Middle Initial & Last Name & Degree
Christine VILLATTE
First Name & Middle Initial & Last Name & Degree
Xavier DURANDO
First Name & Middle Initial & Last Name & Degree
Christophe POMEL
First Name & Middle Initial & Last Name & Degree
Pierre GIMBERGUES
First Name & Middle Initial & Last Name & Degree
Claude DUBRAY
12. IPD Sharing Statement
Learn more about this trial
Memantine and Post-mastectomy Neuropathic Pain
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