Homeopathy on the integrative care of cocaine-related disorders (Cocacrack-3 Study)

Abstract

Background: An effective pharmacotherapy for cocaine use disorder is still needed. Previous results showed a clinically significant difference between the effects of
fifty- millesimal homeopathic potencies of Opium and Erythroxylum coca compared to placebo in reducing cocaine/crack use. Due to the high dropout rate and risk of
bias, further research is required, specifically focusing on strategies to increase patient retention. To further investigate the fifty-millesimal homeopathic potencies of
Opium and Erythroxylum coca on the integrative care of cocaine-related disorders, we had elaborated a study protocol - Cocacrack-3 study protocol, benefiting from
the strengths of primary health care to improve treatment adhesion. However, due to the Covid-19 pandemic, the primary focus of primary care shifted to monitoring
individuals in home isolation and addressing other health needs that had previously been suspended as the death rate began to decline. Due to these circumstances,
we were required to revise the study protocol. We will conduct Cocacrack-3 Study in specialized facilities, using a network support and telemedicine follow-up
approach to enhance adherence.
Objectives: 1) To assess the effectiveness and safety of a sequential administration of homeopathic fifty-millesimal potencies (LM2, LM4, and LM6) of Opium and
Erythroxylum coca in reducing cocaine use among participants. 2) To evaluate the effectiveness of telemedicine and a support network, whether family or otherwise,
in enhancing treatment retention rates among individuals with crack cocaine use disorder.
Setting: Psychosocial Attention Centers for Alcohol and other Drugs (CAPS-AD) located in Florianópolis (both on the island and mainland), São José, and Palhoça,
cities part of the greater Florianópolis area in the state of Santa Catarina, Brazil. The study center is the Research Laboratory for the History of Nursing and Health
Knowledge at the Federal University of Santa Catarina.
Methods design: A randomized, placebo-controlled, double-blind, crossover clinical trial, with six weeks duration per participant.
Hypothesis: H0: There is no clinically significant difference between the effects of fifty-millesimal homeopathic potencies of Opium and Erythroxylum coca
compared to placebo in reducing cocaine use (null hypothesis). H1: There is a clinically significant difference between the effects of fifty-millesimal homeopathic
potencies of Opium and Erythroxylum coca compared to placebo in reducing cocaine use (alternative hypothesis).
Inclusion criteria: men and women between the ages of 18 and 70 who are patients at a participating CAPS-AD, receiving treatment for cocaine use disorder, and
having a support network, whether it be family or otherwise.
Exclusion criteria: remission of cocaine use lasting more than two weeks and inability or unavailability to participate in research in a virtual environment, even with
the support of family or others.
Sample size and crossover sequences: 120 participants will be enrolled and randomized in a 1:1 ratio to one of two sequences - verum for three weeks followed by
placebo for three weeks, or vice versa. Randomization, allocation concealment, and blinding remain unchanged from the original protocol. Interventions: the verum
sequence will consist of LM2, LM4, and LM6 homeopathic potencies of Opium and Erythroxylum coca, used for one week each in ascending order. Opium will be
given in a sucrose globule dissolved on the tongue in the morning, while Erythroxylum coca will be administered in a sucrose globule dissolved on the tongue in the
afternoon and evening, plus an additional globule repeated every hour for six hours in the event of craving. The placebo treatment will consist of sucrose globules
administered in the same dose. Participation in Cocacrack-3 Study will not interfere with the CAPS-AD treatment routine, and all participants, clinical investigators,
CAPS-AD teams, monitors, and statisticians will remain blinded to the study treatments until data analysis is complete.
Primary measure: The percentage of days of cocaine use at week 3, as recorded through telemedicine using a timeline follow-back methodology.

Secondary measures (recorded weekly by telemedicine): The percentage of the reported number of cocaine-using days during participation in the study; change in
participant’s cocaine craving measured through the Cocaine Craving Questionnaire scale - brief; participant’s progression assessed by the Clinical Global Impressions
Scale; use of concomitant medications; occurrence of adverse events; assessment of treatment adherence by the Measure Treatment Adherence scale ; evaluation of
participant retention by the number of participants at weeks 3 and 6; evaluation of study medication use by vial weight at weeks 3 and 6. The effectiveness measures
will be assessed by psychiatrists affiliated with the Federal University of Ceará through telemedicine consultations.
Ethical approval and registration: Cocacrack-3 Study protocol was approved by the Ethics Committee on Human Research at the Federal University of Santa
Catarina. Due to the shift in study implementation from Primary Care, we revised the title to “Homeopathy on Integrative Care for Cocaine-Related Disorders
(Cocacrack-3 Study). After updating the study registry (UMIN Clinical Trials Registry - ID: UMIN000040161), we have scheduled appointments with the study
population (patients and families) and will commence recruitment in early June 2023.