Treatment of Neuropathic Pain in Leprosy

NCT03324035 | Unknown Phase 3 DMC

• 1 other identifier: AmyNeLe
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

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

Conditions

Pain, Neuropathic; Leprosy; Leprosy Neuropathy; Amitriptyline

Outcome Measures

Primary Outcomes (1)

• Reduction in pain intensity of 30% from baseline measured by verbal analog scale (VAS)

  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)

  63 days (9 weeks)

Secondary Outcomes (6)

• Neuropathic pain

  63 days (9 weeks)

• Neuropathic Pain Symptoms

  63 days (9 weeks)

• Mensure Quality of Life

  63 days (9 weeks)

• Number of participants with treatment-related adverse events

  63 days (9 weeks)

• Predictive factor of response

  63 days (9 weeks)

Study Arms (2)

Treatment

EXPERIMENTAL

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; Drug: Tramadol

Placebo

PLACEBO COMPARATOR

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; Drug: Tramadol

Interventions

Amitriptyline DRUG

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.

Treatment

Placebo oral capsule DRUG

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.

Placebo

Tramadol DRUG

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

Placebo; Treatment

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;
• 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;

Sponsors & Collaborators

• University of Sao Paulo: lead
• Cristália Produtos Químicos Farmacêuticos Ltda.: collaborator

Study Sites (1)

Hospital Das Clínicas da Faculdade de Medicina da USP

São Paulo, São Paulo, 05403-010, Brazil

Location

MeSH Terms

Conditions

Neuralgia; Leprosy

Interventions

Amitriptyline; Tramadol

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mycobacterium Infections, Nontuberculous; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Dibenzocycloheptenes; Benzocycloheptenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Dimethylamines; Methylamines; Amines; Lipids

Study Officials

• Daniel Andrade, PhD

  University of Sao Paulo

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Pain Center coordinator, Department of Neurology, University of Sao Paulo, São Paulo, Brazil

Study Record Dates

• First Submitted: June 14, 2017
• First Posted: October 27, 2017
• Study Start: March 1, 2017
• Primary Completion: May 3, 2021
• Study Completion: August 1, 2022
• Last Updated: February 23, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)