Rab 32 Gene Polymorphisms as a Prognostic Factor in Leprosy Patients

Rab 32 Gene Polymorphisms as a Prognostic Factor in Leprosy Patients and Its Relation to Multiple Drug Therapy: Randomized Clinical Trial

Mycobacterium leprae is a slow-growing bacillus that causes leprosy. the infection may take two to ten years to incubate. While the exact mechanism of infection transmission is unknown, direct bacillus absorption through the nasal or respiratory mucosa and aerosolized nasal secretions are the most common theories. The bacteria is subsequently transported by the bloodstream to the peripheral nerves, where it can result in tissue damage from painless burns and ulcers as well as irreparable nerve damage that results in a loss of protective feeling.

Study Overview

• Status: Recruiting
• Conditions: Leprosy; Mycobacterium Leprae Infection
• Intervention / Treatment: Drug: Dapsone

Detailed Description

One of the most common host cells that mycobacteria encounter is macrophages. The process of monocyte-derived macrophages phagocytosing M. leprae is controlled by protein kinase and can be facilitated by complement receptors CR1 (CD35), CR3 (CD11b/CD18), and CR4 (CD11c/CD18). A Th2 cytokine profile appears to be correlated with nonreactivity to M.Leprea.

The Ridley-Jopling classification (1962) divides leprosy into six forms: Tuberculoid (TT), Borderline Tuberculoid (BT), Borderline-borderline Mid-borderline (BB), Borderline-Lepromatous (BL), Subpolar Lepromatous (LLs), and Polar Lepromatous (LLp). These categories are based on clinical, histopathological, and immunological criteria. According to WHO, leprosy is classified into two groups: the paucibacillary (PB) and multibacillary (MB) types, to aid in treatment.

Leprosy is treated as an outpatient procedure using WHO-standardized regimens from 1982, which essentially consist of three first-line medications: clofazimine, rifampicin, and dapsone. This relationship is referred to as polychemotherapy, or MDT (PCT). With minimal bactericidal activity, sulfone (diaminodiphenyl sulfone, or DDS), commonly referred to as dapsone, primarily acts as a bacteriostatic agent.

It most likely functions as an antagonist of para- aminobenzoic acid (PABA), preventing M. leprae from using it to synthesize folic acid. It is well-tolerated and has a number of adverse effects, most of which do not require stopping treatment.

The primary bactericidal effect of rifampicin (RMP), a semi-synthetic derivative of rifamycin B, is observed. It functions by preventing the RNA-polymerase enzyme in the bacillus from growing. RMP has been used to treat leprosy since 1963. Most of the bacilli become non-viable after a few days of therapy, and its use is crucial in all clinical types of leprosy. Clofazimine (CLF) is an iminophenazine dye . It has a mild bactericidal action, acting slowly on M. leprae and destroying 99% of the bacteria in approximately five months. Its efficacy is similar to DDS. CLF has an important anti-inflammatory action.

With an estimated heritability of up to 57%, family studies and community epidemiological surveys have amply established the significant role that host genetics plays in an individual's vulnerability to leprosy.

RAB32 is a low molecular weight G protein belonging to the Ras superfamily. It is necessary for the production of autophagic vacuoles and the control of autophagy's removal of aggregated proteins. Rab32 may play a similar role in the pathogenesis of leprosy, according to a recent study that found the protein controls the recruitment of cathepsin D to phagosomes containing Mycobacterium tuberculosis.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lydia Atef Nassief, MSc; Phone Number: +201289416276; Email: lydiaatef67@gmail.com
• Study Contact Backup: Name: Eisa Mohammed Hegazy, Assist. Prof; Phone Number: +201094337795; Email: eisa_mohamed4152@med.svu.edu.eg

Study Locations

• Egypt
  • Qina, Egypt
    • Recruiting
    • Qina University hospital, South Valley University Hospital
    • Contact: Mohammed Hosny Hassan, Professor; Phone Number: +201098473605; Email: mohammedhosnyhassaan@med.svu.edu.eg
    • Contact: Soheir Abdel-hamid Ali, M.D; Phone Number: +201066877343; Email: Soher.abdel-hamid@med.svu.edu.eg
    • Principal Investigator: Ebtehal Alaa El-din Kotp Mohammed, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients of both sexes with positive slit skin smear for m.leprae .

Exclusion Criteria:

• Contraindications to Multi drug therapy :
• Patients with hypersensitivity to sulfa .
• Patients with hypersensitivity to clofazimine or rifampcin.
• pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group A: Leprosy Patients; About 40 patients suffering from Leprosy and will treated by Multi drug therapy as ( dapsone _ clofazimine _ rifampcin) then to assess the role of Rab 32 gene.by taking Two millimetres of venous blood from each participant At the end of third month therapy.	Drug: Dapsone; To evaluate the effect of the multi drug therapy in leprotic patients and their side effects and to assess the role of Rab 32 gene in leprosy prognosis and to know its association with the multi drug therapy.; Other Names: clofazimine; rifampcin
Active Comparator: Group B: Healthy People; About 10 Healthy People. no drugs used and then to assess the role of Rab 32 gene.by taking Two millimetres of venous blood from each participant	Drug: Dapsone; To evaluate the effect of the multi drug therapy in leprotic patients and their side effects and to assess the role of Rab 32 gene in leprosy prognosis and to know its association with the multi drug therapy.; Other Names: clofazimine; rifampcin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment of leprosy	About 40 of Participants With Treatment-Related Adverse Events as Assessed by measuring the of Rab 32 gene ( Rs2275606 ) polymorphism using real time PCR for Evaluation of the multi drug therapy on Leprotic Patients	6 Months

Collaborators and Investigators

• Sponsor: South Valley University
• Investigators: Study Chair: Eisa Mohammed Hegazy, Assist. Prof, Dermatology, Venereology and Andrology. Faculty of Medicine,South Valley University

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): December 10, 2025
• Study Completion (Estimated): December 20, 2025

Study Registration Dates

• First Submitted: January 21, 2025
• First Submitted That Met QC Criteria: February 4, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 4, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Mycobacterium Infections, Nontuberculous; Leprosy; Anti-Bacterial Agents; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Enzyme Inhibitors; Folic Acid Antagonists; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Leprostatic Agents; Clofazimine; Dapsone
• Other Study ID Numbers: Rab 32 gene polymorphisms

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No