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Efficacy of Duloxetine in Conjunction With Tramadol for Chronic Cancer Pain

Sponsor
Assiut University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05311774
Collaborator
(none)
400
Enrollment
2
Arms
20
Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Cancer pain is one of the most common and problematic symptoms. Opioids are typically the most common drugs used in the treatment of cancer pain,they are limited due to their side effects.

Tramadol is a centrally acting non-opiate analgesic with low affinity for μ-opioid receptors, and is effective in the treatment of moderate to severe pain.

Neuropathic pain is typically not amenable to standard opiate therapy, and the addition of tricyclic antidepressants or/and antiepileptic drugs can offer a very effective treatment strategy in such patients.

Duloxetine is a Serotonin Norepinephrine Reuptake Inhibitor (SNRI) that has been used traditionally for its antidepressant qualities and has also analgesic benefit in the treatment of neuropathic pain. Duloxetine exerts its analgesic action through central and peripheral pain modulation .

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

Cancer pain is one of the most common and problematic symptoms.uncontrolled pain affect quality of life and daily activities .Cancer pain has two main categories nociceptive and neuropathic pain,Cancer pain is often a combination of nociceptive and neuropathic pain.

A framework for managing pain often starts with the World Health Organization (WHO) Analgesic Ladder, step 1 use non opioid analgesics, step 2 weak opioids, step 3 strong opioids, step 4 interventions non pharmacological, adjuvants can be added to any step .

Opioids are typically the most common drugs used in the treatment of cancer pain. They work by binding to μ-opioid receptors within the central nervous system, which are responsible for opioid mediated analgesia, respiratory depression, sedation, physiological dependence, and tolerance, they are limited due to their side effects as nausea, constipation, sedation, and confusion, prolonged use of opioids may lead to development of tolerance, abnormal hypersensitivity to pain.

Tramadol is a centrally acting non-opiate analgesic with low affinity for μ-opioid receptors, and is effective in the treatment of moderate to severe pain. It has been also shown to inhibit reuptake of serotonin and norepinephrine, which synergistically enhances its weak opioid mechanism of action.

This may explain the reduced incidences of abuse, respiratory depression and other adverse effects of traditional opioids in patients on long-term tramadol therapy.it is a useful drug in patients with cancer pain both with nociceptive and neuropathic pain .Neuropathic pain is typically not amenable to standard opiate therapy, and the addition of tricyclic antidepressants or/and antiepileptic drugs can offer a very effective treatment strategy in such patients.

Adjuvant analgesics are drugs primarily marketed for other indications, such as depression, but also have an important role in cancer pain management. Antidepressants, such as serotonin- norepinephrine reuptake inhibitors (duloxetine, venlafaxine) or tricyclics ( nortriptyline, amitriptyline) and anticonvulsants (pregabalin, gabapentin, carbamazepine) have efficacy in the treatment of pain, particularly neuropathic pain .Duloxetine is a Serotonin Norepinephrine Reuptake Inhibitor (SNRI) that has been used traditionally for its antidepressant qualities and has also analgesic benefit in the treatment of neuropathic pain . Duloxetine exerts its analgesic action through central and peripheral pain modulation , it enhances the effect of serotonin and norepinephrine on descending inhibitory pain pathways in the brain and spinal cord and activation of some cerebral prefrontal areas . Besides, it has been claimed that Duloxetine has an anti-nociceptive effect through Na + channel block , therefore it suppresses the neuronal cell firing resulting from peripheral injury . The most common adverse effects of duloxetine, which may lead to discontinuation of the drug, are nausea, dizziness, and somnolence .There is a possibility that duloxetine was effective in both activation of the descending pain modulatory system and the improvement of depressive mood, the effect may have partly taken place due to elevation of the pain threshold through the antidepressant effect of duloxetine . Recently, the efficacy of duloxetine has been reported in patients with chemotherapy-induced peripheral neuropathy (CIPN) and in non-cancer neuropathic pain. .

Study Design

Study Type:
Interventional
Anticipated Enrollment :
400 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Efficacy of Duloxetine in Conjunction With Tramadol for Chronic Cancer Pain
Anticipated Study Start Date :
Apr 1, 2022
Anticipated Primary Completion Date :
Oct 1, 2023
Anticipated Study Completion Date :
Dec 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: •tramadol and duloxetine

patients will receive tramadol 50 mg twice daily, titration will be done every 3days until 2 weeks, maximum dose will be 400mg daily and will receive duloxetine 30mg daily fixed dose in combination with tramadol. Investigators will follow up the patients for 3 months

Drug: Duloxetine 30 mg
tablet
Other Names:
  • cymbatex 30 mg

    • Drug: Tramadol
    tablet
    Other Names:
  • amadol

    		•
    Active Comparator: tramadol and placebo

    patients will receive tramadol 50 mg twice daily, titration will be done every 3days until 2 weeks, maximum dose will be 400mg daily and will receive placebo drug once daily in combination with tramadol. Investigators will follow up the patients for 3 months

    Drug: Tramadol
    tablet
    Other Names:
  • amadol

    • Drug: Placebo
    tablet

    Outcome Measures

    Primary Outcome Measures

    1. concentration of tramadol consumption [at one month]

      all participants(400 patients) will receive tramadol 50 mg twice daily, titration will be done every 3days until 2 weeks,according to changes in visual analogue scale for pain maximum dose will be 400mg daily, one group of participants(200 patients) will receive duloxetine 30mg daily fixed dose in combination with tramadol,decrease in concentration of tramadol consumption means better results,the other group(200 patients) will receive placebo drug once daily in combination with tramadol.

    Secondary Outcome Measures

    1. concentration of tramadol consumption [at 2 month and 3 month]

      all participants(400 patients) will receive tramadol 50 mg twice daily, titration will be done according to changes in visual analogue scale for pain, maximum dose will be 400mg daily, one group of participants(200 patients) will receive duloxetine 30mg daily fixed dose in combination with tramadol,decrease in concentration of tramadol consumption means better results,the other group(200 patients) will receive placebo drug once daily in combination with tramadol.

    2. - change in pain with visual analogue scale [at 3,6,9 and 12 days , 2 weeks,1 month,2 month,3 month]

      subjective scale by the participants for pain intensity from 0 to 10, minimum value is zero that means no pain, maximum value is 10 that means unbearable pain, higher scores mean worse outcome

    3. type of pain that relieved better [at 1 month,2 month and 3 month]

      type of pain that responds better to duloxetine and tramadol (neuropathic or nociceptive), using visual analogue scale for pain intensity (subjective scale by the participants for pain intensity from 0 to 10, minimum value is zero that means no pain, maximum value is 10 that means unbearable pain, higher scores mean worse outcome)

    4. Leeds Assessment of Neuropathic Symptoms and Signs Scale if neuropathic pain [at 1 month,2 month and 3 month]

      used for neuropathic pain consists of seven questions minimum value 0 ,maximum value 24,scoring a score of 12 or more suggests pain of predominantly neuropathic origin

    5. Scale Assessing Pain Intensity and Interference (Pain, Enjoyment, General Activity) [at 1 month,2 month and 3 month]

      consisting of three questions for the participant,responses from 0 to 10 ,responses to three questions added then divided by three to get a mean score out of ten

    6. Depression scores by the Patient Health Questionnaire [at 1 month,2 month and 3 month]

      consists of 9 questions for the participant ,This is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of "not at all," "several days," "more than half the days," and "nearly every day," respectively, total score for the nine items ranges from 0 to 27,higher scores means worse outcome

    7. Anxiety scores by the Patient Health Questionnaire [at 1 month,2 month and 3 month]

      consists of 7 questions for the participant ,This is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of "not at all," "several days," "more than half the days," and "nearly every day," respectively, total score for the seven items ranges from 0 to 21,higher scores means worse outcome

    8. Flanagan Quality of Life Scale [at 1 month,2 month and 3 month]

      consists of 16 items ,seven responses are delighted(7),pleased(6),mostly satisfied(5),mixed(4),mostly dissatisfied (3),unhappy(2),terrible(1),ranging from 16 to 112,average for healthy 90

    9. Side effects as nausea, vomiting, constipation, sedation, arrhythmia and hypertension [up to 3 month]

      participants will be asked about side effects from duloxetine as nausea,vomiting, constipation, sedation, (onset,duration,offset, bearable or not ,affecting quality of life), arrhythmia (type of arrhythmia from electrocardiogram ,onset,duration,offset),hypertension (by measuring blood pressure ,onset ,duration ,offset)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients with cancer pain

    1. age from 20-70 years old.

    2. not receiving any type of analgesia before (opioid naïve, no adjuvants).

    Exclusion Criteria:

    1. Difficult to be assessed for pain.

    2. Any contraindication for duloxetine or tramadol.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Assiut University

    Investigators

    • Study Director: khaled M Fares, MD, Assiut University
    • Study Director: Ahmad M Abd EL Rahman, MD, Assiut University
    • Study Director: Diab F Hetta, MD, Assiut University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Madona M.NOMAN, Doctor, Assiut University
    ClinicalTrials.gov Identifier:
    NCT05311774
    Other Study ID Numbers:
    • Duloxetine in cancer pain
    First Posted:
    Apr 5, 2022
    Last Update Posted:
    Apr 5, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Madona M.NOMAN, Doctor, Assiut University
    duloxetine
    tramadol
    cancer pain
    Additional relevant MeSH terms:
    Cancer Pain
    Duloxetine Hydrochloride
    Tramadol

    Study Results

    No Results Posted as of Apr 5, 2022