Leprosy

Researchers are evaluating the safety, tolerability, and how the body processes (pharmacokinetics) single and multiple intravenous doses of a drug called BWC0977 in healthy adult volunteers. This Phase 1 study involves a total of 64 healthy adults aged 18 to 55 years and is designed as a randomized, double-blind, placebo-controlled trial with multiple dose groups. The study focuses on measuring any treatment-emergent adverse events and serious adverse events to understand the drug's safety profile. Participants will be divided into two main groups: single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. In the SAD phase, volunteers receive one intravenous infusion of BWC0977 or placebo over 2 hours at doses of 750 mg or 1500 mg. In the MAD phase, participants receive multiple intravenous infusions of BWC0977 or placebo over 30 minutes to 2 hours daily for 7 to 10 consecutive days. Dose levels will increase sequentially based on safety and tolerability data collected during the study. During the study, participants will undergo various assessments including physical exams, vital signs, ECGs, laboratory tests, and blood sampling at specific times before, during, and after infusions to monitor safety and measure drug levels in the body. Researchers will track adverse events for up to 8 days after single dosing and up to 16 days after multiple dosing. Volunteers must comply with study visits and requirements throughout the trial, which lasts until August 2026.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae or Mycobacterium lepromatosis, mainly affecting the peripheral nerves and leading to neurological damage, disability, and deformities if not diagnosed and treated early. This research evaluates the diagnostic and prognostic accuracy of combining clinical evaluation, peripheral nerve ultrasonography, and molecular detection techniques using ultrasound-guided perineural subcutaneous aspirate. The goal is to improve early detection and monitoring of leprosy compared with traditional methods like bacilloscopy and biopsy. Participants with suspected leprosy will undergo clinical exams, high-resolution ultrasound of the ulnar nerves, and an ultrasound-guided subcutaneous aspirate near the nerve. This aspirate is tested using real-time PCR and RT-PCR to detect DNA and RNA of Mycobacterium leprae, which may help identify viable bacteria. The study involves assessments at diagnosis and after one year of treatment to compare findings and evaluate the new diagnostic method's accuracy. Throughout the one-year study, participants will have clinical and imaging evaluations, molecular testing of aspirated material, and monitoring of nerve changes. Researchers will measure the diagnostic accuracy of the molecular tests and correlate ultrasound findings with molecular results. This approach aims to develop improved, less invasive diagnostic workflows that can be used in public health settings to reduce disease transmission and long-term disability.

Researchers are evaluating a new approach to prevent leprosy in people living near someone recently diagnosed with the disease. This phase 3 randomized study compares two treatments: a combination of bedaquiline and rifampicin (BE-PEP) versus the World Health Organization's standard single-dose rifampicin (SDR-PEP). The goal is to assess which method better reduces the risk of developing leprosy and lowers the overall number of cases over time. Participants will be assigned to one of two groups. In the intervention group, BE-PEP—bedaquiline at 400 or 800 mg depending on weight combined with rifampicin at 10 mg/kg—is given to individuals living within 100 meters of an index case, with a repeat dose after four weeks for household contacts. The comparison group receives the standard single dose of rifampicin at 10 mg/kg. If more than half the village is eligible, the entire village is included. Treatment delivery uses specific dosage forms of rifampicin and bedaquiline, and the study started providing BE-PEP in 2023, with follow-up planned through 2026. During the study, participants are monitored for leprosy development and possible side effects such as nausea, headache, dizziness, or skin reactions up to 30 days after treatment. Researchers collect skin biopsies from leprosy patients to check for drug resistance using molecular tests and monitor tuberculosis patients for similar resistance patterns. The main outcome measured is the rate of leprosy cases between the two groups over about four years, alongside a village-level impact assessment. The study aims to provide a safe and effective prevention strategy and support future national guideline updates.

Researchers are studying dovramilast, an experimental drug not yet approved for leprosy type 2 reaction (erythema nodosum leprosum, ENL), to compare its effects with current standard treatments. The study focuses on adults with moderate to severe acute or recurrent leprosy type 2 reaction to evaluate the safety and efficacy of two doses of dovramilast, 100 mg and 150 mg. This Phase 2 trial aims to understand how well these doses improve skin lesions and assess any adverse effects. Participants will be randomly assigned to receive either 100 mg or 150 mg of dovramilast or standard care, which includes prednisolone or thalidomide (in US sites only). The treatment period lasts 12 weeks, during which the responses to these interventions are monitored. The study is open-label, meaning both researchers and participants know which treatment is given. The trial includes a dose-ranging design to evaluate different strengths of dovramilast. During the 12-week trial, participants will undergo assessments including skin lesion evaluations, fever resolution, and neuropathy changes. Researchers will use the ENLIST severity scale and monitor the need for rescue medications. Safety is closely monitored by tracking adverse events. Additional follow-up up to 48 weeks will assess recurrences and drug exposure. Participants will be regularly evaluated with laboratory tests and photographic assessments to measure outcomes and ensure adherence.

Researchers are evaluating the safety, tolerability, and effectiveness of adding metformin to standard multidrug therapy (MDT) for patients newly diagnosed with multibacillary leprosy. This double-blind, placebo-controlled Phase 2 trial aims to see if metformin can reduce leprosy reactions, nerve damage, and corticosteroid use while assessing immunological responses. The study is supported by the Leprosy Research Initiative and conducted in Indonesia with participants aged 18 to 65. Participants will be randomly assigned to receive either metformin or a placebo once daily. Metformin dosing starts at 500mg for two weeks, then increases to 1000mg for 22 weeks, alongside 48 weeks of standard MDT. The placebo group receives matching tablets to maintain blinding. The trial plans to enroll 166 patients to compare clinical outcomes between the two groups. During the 48-week study, participants will be regularly monitored for leprosy reactions, adverse events, nerve function, corticosteroid use, and quality of life through clinical assessments and questionnaires. The primary outcomes include the proportion of patients experiencing leprosy reactions and adverse events within specified timeframes. Secondary outcomes focus on reaction severity, timing, frequency, and impact on daily living. Safety and tolerability will also be closely observed throughout the study period.

Researchers are evaluating how experiencing awe influences adults' willingness to engage in prosocial preventive behaviors against infectious diseases. This randomized controlled trial includes adults from Hong Kong, Singapore, and ten major cities in Mainland China. The study aims to find out if feeling awe can increase intentions for actions like vaccination, mask-wearing, and social distancing, and whether these effects differ by location. Participants will be randomly assigned to one of two groups. The intervention group will play a three-step mini game called Hidden Picture Puzzle designed to induce awe by revealing nature scenes and reflecting on feelings evoked. The control group will play the same game format but will uncover everyday objects and describe their features instead. Each participant will complete four rounds of the game with different images. During the study, participants will complete the game and immediately report their intentions to engage in preventive behaviors and their choices in pandemic-related scenarios. The study will also assess intentions to participate in social activities after the game. The trial is conducted online, and participants had a baseline assessment about four months before the trial. The research team will monitor responses immediately after the game to measure the impact of awe on prosocial behavior.

Researchers are conducting a national, multicenter prospective study to understand how genetic defects and autoantibodies against type I interferons (IFNs) affect the immune response to infections, especially severe viral diseases like COVID-19. This study focuses on adults who either have inborn errors of immunity (IEI) impairing type I IFN responses or carry neutralizing autoantibodies against type I IFNs, which have been linked to severe illness and increased mortality in COVID-19. The aim is to track infectious, autoimmune, and cancer-related events to improve prevention and management strategies for these patients. The study includes adults with these immune characteristics who may be patients with past or current disease or healthy individuals such as blood donors or relatives of affected patients. Participants will have yearly visits to clinical centers for blood sampling and medical history updates, including investigations of immune markers, autoantibodies, and genetic analyses. Additional visits occur if participants experience infections, autoimmune flare-ups, cancer diagnoses, or COVID-19 infections, with detailed blood tests and teleconsultations. Controls without these immune abnormalities will be matched and followed through questionnaires and health data linkage. Participants undergo an initial visit to collect demographic information, medical and family history, and blood samples for detailed immune and genetic tests, including whole-exome or whole-genome sequencing. Follow-up visits occur annually for up to four years, involving clinical assessments and blood sampling to measure autoantibody levels and immune function. Clinical events and healthcare use will be tracked through national health data, and the main outcomes include measuring autoantibody levels and their neutralizing activity over time. This long-term monitoring aims to reveal factors influencing disease risk and immune changes in this population.

Researchers are evaluating whether a multifactorial active case-finding strategy can improve the detection of leprosy cases in Brazil compared to standard screening methods. The study aims to find out if this intervention increases the number of new leprosy cases identified and to better understand underdiagnosis as well as the clinical profiles of diagnosed patients. Healthcare professionals will also receive training to enhance leprosy detection in primary care units. The intervention includes raising community awareness about leprosy, training health workers, using georeferencing tools to identify priority areas, and applying a Leprosy Suspicion Questionnaire to screen people in these areas. Those with positive questionnaire responses will undergo clinical evaluation by a trained medical team. If leprosy is diagnosed, additional laboratory tests will be collected. The study compares this active case-finding approach to routine screening practices. Participants will be involved through community screening and clinical evaluations, with data monitored over a 12-month period using Brazil's national notification system. Researchers will assess new leprosy cases from the time of a positive questionnaire until confirmation or ruling out of leprosy within two months. They will also evaluate the usefulness of the Leprosy Suspicion Questionnaire and rapid test during this period. The study will provide important insights into leprosy detection and diagnosis in affected communities.

Researchers are investigating new ways to prevent leprosy by focusing on people who have been in contact with individuals infected by Mycobacterium leprae. The study evaluates the effect of a single dose or a double dose of the antibiotic rifampin given after exposure to prevent infection. It also uses a new, simple blood test called UCP-LFA to detect signs of infection early, helping to guide treatment decisions and potentially stop the spread of the disease in communities where leprosy remains common. The trial compares two dosing strategies of rifampin given to household contacts and close neighbors of newly diagnosed leprosy patients. Adults and children 5 years and older receive either a single dose or a double dose of rifampin adjusted by weight. The study uses the UCP-LFA test to measure immune markers related to M. leprae infection before and after the treatment to assess changes. This approach aims to improve early detection and prevention efforts in field settings. Participants are monitored through blood samples taken before and at 2 weeks, 4 weeks, and 6 months after receiving rifampin. These samples help track changes in immune proteins and bacterial load to evaluate the impact of the prophylactic treatment. The study involves regular follow-ups to assess effectiveness and safety, with a focus on practical, point-of-care testing methods that can be used widely in endemic areas. The total duration of participant involvement spans at least 6 months after intervention.

Researchers are investigating the effects of pre-operative mouthwash and varying oxygen levels during surgery on the rates of pneumonia and surgical site infections in patients undergoing major abdominal surgery. This trial focuses on patients in low and middle-income countries, where postoperative complications are more common and often more severe. The study aims to find ways to reduce these serious complications, which can cause pain, disability, and increased healthcare costs. Participants will be randomly assigned to one of four groups: pre-operative chlorhexidine mouthwash combined with high oxygen levels (80-100% FiO2), no mouthwash with high oxygen levels, mouthwash with low oxygen levels (21-30% FiO2), or no mouthwash with low oxygen levels. Treatments are given around the time of surgery, with oxygen delivered during the operation and mouthwash used before surgery. The study includes an internal pilot phase lasting six months to check recruitment and compliance, followed by a larger trial aiming to enroll nearly 13,000 participants. During the study, researchers will monitor participants for up to 30 days after surgery, assessing rates of pneumonia and surgical site infections using CDC definitions. They will also track other outcomes like mortality, repeat surgeries, hospital stay length, return to normal activities, critical care admissions, and healthcare resource use. Follow-up includes evaluating patient recovery and safety, with all data collected to understand how these interventions impact surgical outcomes in these settings.