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Treatment of Neuropathic Pain in Leprosy (AmyNeLe)

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ClinicalTrials.gov Identifier: NCT03324035
Recruitment Status : Recruiting
First Posted : October 27, 2017
Last Update Posted : December 28, 2020
Sponsor:
Collaborator:
Cristália Produtos Químicos Farmacêuticos Ltda.
Information provided by (Responsible Party):
Daniel Ciampi Araujo de Andrade, MD, PhD, University of Sao Paulo

Brief Summary:
Despite large efforts to eradicate leprosy, this curable mycobacterial infection still affects 250,000 new individuals annually. Half of the globe's leprosy patients live in Brazil and India. In 2013, 33,033 new leprosy cases diagnosed in Brazil, with an average incidence of 1.05 cases / 10 000 inhabitants. Recently a new concept of care after cure has called attention for severe pain in previously treated patients, particularly, neuropathic pain. Even so, until now no single drug has been studied for the treatment of pain in this patients, and the use of drugs is based on the study of other diseases. We designed the first placebo-controlled, double blinded randomized trial in the use of flexible-dose amitriptyline (tricyclic antidepressant) for the treatment of neuropathic pain related to leprosy

Condition or disease Intervention/treatment Phase
Pain, Neuropathic Leprosy Leprosy Neuropathy Amitriptyline Drug: Amitriptyline Drug: Placebo oral capsule Drug: Tramadol Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 102 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment of Neuropathic Pain in Leprosy: a Randomized Double Blind Controlled Study
Actual Study Start Date : March 1, 2017
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2021

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Leprosy

Arm Intervention/treatment
Experimental: Treatment
Patients on this arm will receive amitriptyline on flexible doses, starting from 25mg (1 capsule) and titrated to 50mg (2 capsules) or 75mg (3 capsules), based on brief pain inventory (BPI) questionnaire, applied weekly for 3 consecutive weeks. All patients will receive tramadol as a supportive drug for the treatment of neuropathic pain, they are instructed to take 50mg every 8 hours, if pain present.
Drug: Amitriptyline
Administer amitriptyline on flexible doses variating from 25mg to 75mg, with backup of tramadol, and evaluate the reduction of the pain based on the Brief Pain Inventory Questionnaire.

Drug: Tramadol
Administer to both arms on "as needed" scheme, to a maximum of 150mg/day.

Placebo Comparator: Placebo
Patients on this arm will receive placebo on flexible doses, starting from 1 capsule and titrated to 2 capsules or 3 capsules, based on brief pain inventory (BPI) questionnaire, applied weekly for 3 consecutive weeks. All patients will receive tramadol as a supportive drug for the treatment of neuropathic pain, they are instructed to take 50mg every 8 hours, if pain present.
Drug: Placebo oral capsule
Administer amitriptyline on flexible doses variating from 1 to 3 capsules, with backup of tramadol, and evaluate the reduction of the pain based on the Brief Pain Inventory Questionnaire.

Drug: Tramadol
Administer to both arms on "as needed" scheme, to a maximum of 150mg/day.




Primary Outcome Measures :
  1. Reduction in pain intensity of 30% from baseline measured by verbal analog scale (VAS) [ Time Frame: 63 days (9 weeks) ]
    To evaluate the analgesic effect of amitriptyline in flexible dose in patients with neuropathic pain associated with leprosy compared to placebo on the Visual Analogic Scale (VAS) (range 100mm- minimum 0 and maximum 100)


Secondary Outcome Measures :
  1. Neuropathic pain [ Time Frame: 63 days (9 weeks) ]
    DN4 (douleur neuropathique 4) + (≥ 4/10)

  2. Neuropathic Pain Symptoms [ Time Frame: 63 days (9 weeks) ]
    To assess the effectiveness of amitriptyline on the reduction of painful symptoms, and on neuropathic dimensions evaluated by the NPSI questionnaire (minimum 0 and maximum 100)

  3. Quality of Life [ Time Frame: 63 days (9 weeks) ]
    To assess the impact of amitriptyline on the patient's quality of life, depressive and anxiety symptoms, quality of sleep, through the WHOQOL questionnaire (range 0 to 100).

  4. Number of participants with treatment-related adverse events [ Time Frame: 63 days (9 weeks) ]
    To evaluate the number of participants with treatment-related adverse events as assessed by CTCAE v4.03 score 0/1 vs 2/3/4

  5. Predictive factor of response [ Time Frame: 63 days (9 weeks) ]
    assess whether pain phenotype A (NPSI baseline score <15) responded differently to the active drug compared to phenotype B (NPSI score at baseline ≥ 15)

  6. Use of backup pain medication [ Time Frame: 63 days (9 weeks) ]
    To assess the difference in dosage of rescue medication (tramadol) between both treatment arms, by counting the number of pills of tramadol used by each patient.



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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Presence of spontaneous pain of medium intensity in the last 24 hours with a minimum value of 4 in 10 on a numerical scale, with a maximum of 10 points (summed pain questionnaire)
  • Duration of pain of at least 6 months
  • Presence of neuropathic pain "pure" or of clearly dominant character (no other pain, or pain associated unimportant)
  • Pain due to leprosy confirmed by clinical examination and / or appropriate electrophysiological examination
  • Ability to properly understand the Portuguese language, being able to understand the methodology of the study and questionnaires
  • Having provided their consent in writing of their participation in the study

Exclusion Criteria:

  • Linked to the disease in study:
  • Neuropathic pain from other causes that not Hansen's disease (Diabetes, HIV, and after chemotherapy);
  • Linked to the treatment:
  • Hypersensitivity to amitriptyline and tramadol;
  • Ongoing treatment with monoamine oxidase inhibitors (MAOIs);
  • Cardiac and ophthalmologic disorders that contraindicate the use of amitryptiline;
  • Pregnant or nursing women, or even women of childbearing age without the use of contraceptives.
  • General
  • Other pain with intensity higher then the neuropathic one;
  • Ant other condition that may interfere with the evaluation of the study;
  • Patients who have not given or signed the informed consent form;
  • Incorrectly completion of the self-assessment of pain notebook in the period between inclusion and randomization (at least 4 scores in 7 days);
  • Patients who can't be followed on a regular basis or that miss the appointments (we will give a 7 day tolerance for each appointment);
  • Documented abuse of psychoactive drugs or alcohol;
  • History of past or actual psychosis;
  • Actual diagnosis of major depression following the DSM-IV criteria;
  • Language and cognitive deficits that are capable of interfering with the understanding of the study;
  • Patients not affiliated with a social security scheme (beneficiary or recipient);
  • Patients who refuses to sign or are unable to understand the informed consent, under guardianship;
  • Participation in other research protocol involving the use of any medication during the 30 days preceding the inclusion in the project.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03324035


Contacts
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Contact: Renato Pazzini, MD 5511974429181 renatopazzini@me.com
Contact: Daniel Andrade, PhD 5511997753538 ciampi@usp.br

Locations
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Brazil
Hospital Das Clínicas da Faculdade de Medicina da USP Recruiting
São Paulo, SP, Brazil, 05403-010
Contact: Renato Pazzini, MD    5511974429181    renatopazzini@me.com   
Contact: Daniel AC Andrade, PhD    5511997753538    ciampi@usp.br   
Sub-Investigator: Maria AB Trindade, PhD         
Sub-Investigator: Gil Bernard, PhD         
Sub-Investigator: Antonia LL Rodrigues         
Sub-Investigator: Ricardo Galhardoni, PhD         
Sub-Investigator: Manoel J Teixeira, PhD         
Sub-Investigator: Wagner Galvão, MD         
Sub-Investigator: Renato Pazzini, MD         
Principal Investigator: Daniel AC Andrade, PhD         
Sub-Investigator: Valquiria A Silva         
Sponsors and Collaborators
University of Sao Paulo
Cristália Produtos Químicos Farmacêuticos Ltda.
Investigators
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Principal Investigator: Daniel Andrade, PhD University of Sao Paulo
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Responsible Party: Daniel Ciampi Araujo de Andrade, MD, PhD, Principal Investigator, Pain Center coordinator, Department of Neurology, University of Sao Paulo, São Paulo, Brazil, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT03324035    
Other Study ID Numbers: AmyNeLe
First Posted: October 27, 2017    Key Record Dates
Last Update Posted: December 28, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Leprosy
Neuralgia
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Pain
Neurologic Manifestations
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Tramadol
Amitriptyline
Amitriptyline, perphenazine drug combination
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antidepressive Agents, Tricyclic
Antidepressive Agents
Psychotropic Drugs
Analgesics, Non-Narcotic
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents