Clinical trials

In India, lung cancer is the 2nd most common in males and 4th overall in cancer incidence with 81,784 new cases and 75,031 deaths with a 5-year prevalence of 1,13,990 as per GLOBOCAN 2022. Air pollution, particularly fine particulate matter (PM2.5), has been identified as a significant risk factor for lung cancer in never-smokers. India is showing an increasing incidence of lung cancer and there is a need to understand air pollution given many cities in India have been reported to be the most polluted in the world. Evidence of causal associations between PM2.5 and an increased likelihood of lung cancer with underlying biological mechanisms are now fully known. Current evidence focuses on individual pollutants, overlooking potential interactions among multiple risk factors that could amplify lung cancer risks. There is paucity of data on vulnerability of groups like children, older adults, and individuals with pre-existing health conditions, who may face disproportionate risks from poor air quality. The long-term effects of chronic exposure to air pollutants and their cumulative contribution to lung cancer risk remain understudied. Centre for Advanced Research on AIRCARE is essential to bridge these research gaps, providing a holistic understanding of air pollution's role in lung cancer to plan prevention and policy strategies. The study will be conducted at AIIMS, Delhi, and areas in Delhi and NCR with varying levels of PM 2.5 exposure and will encompass regions with diverse socio-economic profiles and industrial activities to capture the heterogeneity of exposure and risk. Subjects and controls will be enrolled to ensure a suitable representation of various demographic, socio-economic and air pollution exposure parameters. A subset of the cohort will be selected for genotyping, focusing on individuals with extreme exposure levels and/or lung cancer cases and controls for genetic interaction studies.

The study is a prospective, randomized, non-inferiority clinical trial which will test whether a short course of radiation treatment (hypofractionation) for cervical cancer works as well as the standard longer course. Cervical cancer is one of the most common cancers in women in India, and many patients have trouble completing treatment because it takes several weeks and requires many hospital visits. In this trial, females with locally advanced cervical cancer will be randomly assigned to one of two treatment groups. One group will receive the standard radiation schedule with External Beam RadioTherapy (EBRT) over about 5 weeks, weekly cisplatin chemotherapy, and brachytherapy. The other group will receive a shorter, hypofractionated external beam radiotherapy schedule over about 3 weeks, the same chemotherapy, and brachytherapy. Researchers will compare the two groups to see whether the hypofractionated schedule is non-inferior to the standard radiation therapy schedule. The main outcomes will be tumor control in the pelvis, side effects, survival, and quality of life. If the hypofractionated schedule meets the non-inferiority limit, it could reduce treatment time, improve patient convenience, and help more people receive treatment in busy cancer centers in emerging countries.

Cervical cancer is a significant cause of morbidity and mortality among women worldwide. Radiotherapy, in combination with chemotherapy or as a standalone treatment, is an effective treatment option for cervical cancer. However, traditional radiotherapy has its limitations, such as the potential for damage to surrounding healthy tissues. Stereotactic Body RadioTherapy (SBRT) is a newer radiotherapy technique that delivers high doses of radiation to the tumor with minimal damage to the surrounding tissues. This study aims to evaluate the safety of Stereotactic Body RadioTherapy to involved node in cervical cancer.

The GLOBOCAN 2022 report for India, suggests lung cancer as the second most frequent cancer in males, with a case count at 58,970 forming 8.5% of the entire cancer burden for males in India. Upon including females, lung cancer still figures in the top five (ranked 4th) most frequent cancers in the country with 81,748 cases which is 5.8% of the entire case load of cancer in India. LDCT is the only test to screen for lung cancer recommended by various associations including USPSTF for the high-risk smokers in 50-80 years. There is no conclusive data on the efficacy of LDCT in screening lung cancer in the Indian population and the care pathways which might exist for individuals so diagnosed. There is a severe lack of evidence in accounting for the utility of LDCT in screening lung cancer in India, which is largely formed by underpowered retrospective results. This study will employ a prospective, cohort design in order to evaluate the efficacy of LDCT screening for lung cancer in a high-risk Indian population. The subject will receive a relevant and prompt Multidisciplinary team (MDT) referral if any LDCT scan is found to raise suspicions for cancer. The effective management of lung cancer relies heavily on timely diagnosis, streamlined care pathways and coordinated multidisciplinary treatment approaches. This project also aims to systematically evaluate the existence or absence of formalized care pathways for lung cancer patients within the Indian healthcare system, as part of a broader initiative assessing LDCT screening utility. The project will explore the current referral systems, diagnostic workflows, multidisciplinary team involvement, treatment initiation processes, and follow-up mechanisms. By mapping these pathways, the study will identify key bottlenecks, gaps, and regional disparities affecting patient journeys from suspicion or diagnosis through treatment and survivorship.

Hypo-fractionated radiotherapy reduces the OTT (overall treatment time) which may in turn reduce rapid accelerated repopulation of clonogenic cells during waiting period after surgery. If this holds true, there is a potential to achieve better loco-regional control in with PORT for HNSCC. There is a strong radiobiological and economic rationale for delivery hypo-fractionated radiotherapy in HNSCC. The HYPCON III trial will be aimed to reduce the number of fractions by 50% (30 fr to 15 fr)

The aim of the study is to test the feasibility \& loco-regional control rate by combining high precision SBRT with chemotherapy in stage III NSCLC in tumor/lymph nodes if tumors/lymph node size with ≤ 6cms in size.

The present study is a phase II/III prospective randomized trial designed to determine whether eliminating of post operative radiotherapy to regional lymphatics in pN0-N1oral cavity is associated with similar treatment outcomes.

The aim of SWOAR TRIAL is to test sparing of Dysphagia/ Aspiration risk structures (DARS) and contra lateral submandibular gland by IMRT. HNSCC of the oropharynx, larynx and the hypopharynx treated with radical concurrent chemoradiotherapy or radiotherapy will be included in the trial. Patients will be randomized to SWOAR IMRT or standard IMRT. Swallowing function will be evaluated the MD Anderson Dysphagia Inventory (MDADI) scoring. Difference in the mean composite score of MDADI, a patient-reported outcome, at 6 months post radiotherapy is the primary outcome of the trial. Secondary Objectives include longitudinal assessment of aspiration prevention as evaluated by FEES by the 8 point penetration-aspiration score. Swallowing function, will be assessed by using the MDADI at baseline, at completion of CRT/RT, 3, 6, 12, and 24 months. Assessment of acute and late toxicity assessed at baseline, weekly during radiotherapy and then at 3, 6, 12, and 24 months post treatment as per RTOG and LENT SOMA score, respectively. Treatment outcomes will be assessed in terms of loco-regional tumor recurrence and overall survival, assessed at follow-up visits 3, 6, 12, and 24 months post treatment and then annually until 5 years post treatment.

Perinatal depression (PND), defined as a depressive episode occurring from the antenatal period through 12 months following childbirth, has a reported prevalence of 12-22%, with higher rates in low- and middle-income countries (LMICs) including India. PND has a multifaceted and detrimental impact on both the mother and the child during a critical window of the child's emotional, cognitive, and physical development. Mother-infant bonding - the affective relationship that develops between a mother and her infant - is significantly impaired by maternal depression. Impaired bonding leads to poor antenatal attachment, earlier cessation of breastfeeding, risk of child maltreatment and neglect, and diminished reciprocal emotional and cognitive growth in the infant. The maternal brain undergoes significant neurobiological adaptations during the perinatal period to facilitate recognition of infant emotional cues, reward-driven bonding experiences, and reciprocal emotional responses. These include changes in oxytocin signalling, cortisol regulation, and functional connectivity of brain regions involved in maternal behaviour. Perinatal depression disrupts these neurobiological processes. Yoga-based interventions offer a safe, cost-effective, culturally acceptable, non-pharmacological approach. Yoga has demonstrated efficacy in improving depression and anxiety in perinatal populations. Its mechanisms include modulation of the HPA axis, reduction of cortisol, enhancement of oxytocin release, and promotion of mindful interoceptive awareness - directly relevant to the neurobiological disruptions in PND. This randomised controlled trial evaluates the efficacy of a structured 3-week bedside yoga intervention as an add-on to treatment as usual in improving mother-infant bonding scores, depression scores, and peripheral oxytocin and cortisol levels in mothers with perinatal depression. The study additionally explores the baseline neural correlates of mother-infant bonding using Event Related Potentials (ERP) and functional MRI (fMRI) of the brain.

AIM: To compare the efficacy of a Novel calcium silicate doped treated dentin matrix and Mineral Trioxide aggregate as biomaterials for miniature pulpotomy. OBJECTIVES: Primary objective: To evaluate the efficacy of calcium silicate-doped human-treated dentin matrix (CaSi+hTDM) compared to Mineral Trioxide Aggregate (MTA) in maintaining pulp vitality using cold testing following Miniature Pulpotomy (MP) in deep and extremely deep carious lesions with reversible pulpitis in 14- to 35-year-old patients reporting to Department of Dentistry, AIIMS Nagpur. Secondary objectives: 1. To evaluate patient-reported outcomes such as pain, swelling, sinus tract etc. post-operatively. 2. To determine the clinical success rates of both materials by assessing the Periapical index of healing over a 6 months follow-up period. NULL HYPOTHESIS: The null hypothesis (H0) is that there is no difference between CaSi+hTDM and MTA in maintaining pulp vitality when used as a Miniature Pulpotomy (MP) biomaterial in carious lesions.

This study will evaluate the effect of the yoga in participants with chronic insomnia. The primary objective is to determine whether adding yoga to standard care improves insomnia severity, as measured by the Insomnia Severity Index (ISI), compared to standard care alone. The study will also assess changes in sleep architecture using polysomnography and examine dysfunctional beliefs and attitudes about sleep. Secondary objectives include evaluating the effects of yoga on stress biomarkers (salivary cortisol and salivary alpha-amylase) and on somatosensory information processing using quantitative sensory testing. These measures aim to explore possible mechanisms by which yoga may influence insomnia symptoms, including stress modulation and sensory processing changes. This assessor-blinded, randomized controlled trial will enroll 72 participants aged 18-65 years diagnosed with chronic insomnia. Participants will be randomly assigned to one of three groups: (1) Yoga + Standard Care (2) Stretching group + Standard Care (3) Standard Care alone. The yoga group and stretching group will receive an 8-week intervention (2 weeks supervised group sessions, followed by 6 weeks home practice with telemonitoring). Assessments will be performed at baseline, 2 weeks, and 8 weeks. The primary outcome is change in ISI score at 8 weeks. Secondary outcomes include polysomnographic measures, dysfunctional beliefs and attitudes about sleep, depression-anxiety-stress scores, daytime sleepiness, stress biomarker levels, and sensory thresholds

Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colon and rectum, characterized by mucosal inflammation and symptomslike diarrhea, abdominal pain, and rectal bleeding. It is a subtype of inflammatory bowel disease (IBD) and results from a combination of genetic predisposition, environmental factors, and immune dysregulation. UC is associated with significant gut microbiota dysbiosis, marked by reduced beneficial bacteria and increased harmful taxa. With rising prevalence in developing countries like India, effective and accessible treatments remain a critical need. This multi-center randomized factorial double blind placebo controlled treat through trial will utilize a 2x 2 factorial design to randomize patients of mild to moderate (modified Mayo score 3-6) endoscopically active (Mayo endoscopic score: \>1) treatment naÃive UC in 1:1:1:1 ratio to fecal microbiota transplantation (FMT) + anti-inflammatory diet (AID) +5-aminisalicylic acid (5-ASA) (Intervention, Group A) vs fecal microbiota transplantation + sham diet +5-aminisalicylic acid(Intervention, Group B) vs sham transplantation + anti-inflammatory diet +5-aminisalicylic acid(Intervention, Group C) vs sham transplantation \+ sham diet +5-aminisalicylic acid(Control, Group D). In the induction phase patients will receive FMT/sham transplantation at 0, 2 and 6 weeks along with AID/Sham diet and 5-ASA for 10 weeks. Outcome will be assessed at 10 weeks, Treatment failure will be out of trial. Patients with clinical response at 10 weeks will continue in the maintenance phase and will receive FMT/sham transplantation at 10, 18, 26, 34, and 42 weeks along with AID/Sham diet and 5-ASA till48 weeks. Outcome will be assessed at 48 weeks. Treatment failure will be out of trial. The primary efficacy outcome will evaluate fecal microbial transplantation or anti- inflammatory diet or combination of both vs placebo. The primary outcomes are proportion of patients having clinical remission and endoscopic response at week 10 and proportion of patients having clinical remission and endoscopic remission at week 48. Modified intention to treat analysis will be done and patients who receive at least 1 dose of intervention will be included for outcome assessment.

Advanced therapies including biologics and small molecules target specific inflammatory pathways. IBD's multifactorial etiology means that blocking a single pathway may not be sufficient for all patients. Even when combination of advanced therapies are used, the incremental benefits often diminish, reflecting the therapeutic ceiling. Furthermore, safety concerns also limit the potential to push beyond this ceiling. Increasing the dose or adding more immunosuppressive agents can lead to a higher risk of infections, malignancies, and other adverse effects, making it impractical to continually intensify treatment. Understanding the therapeutic ceiling in IBD highlights the need for innovative approaches that go beyond current strategies. Given the diverse microbial and immunological landscapes in IBD combining fecal microbiota transplantation (FMT) and Crohn's Disease Exclusion Diet (CDED) with advanced therapies represents a promising approach to break the therapeutic ceiling in CD. This strategy leverages the complementary mechanisms of action of FMT/CDED and advance therapies, potentially offering a more comprehensive treatment modality that addresses the complex and multifactorial nature of IBD. FMT involves the transfer of gut microbiota from a healthy donor to a patient, aiming to restore a balanced microbial community in the intestines. This can help modulate the immune system and reduce inflammation, which are central to Crohn's disease pathology. This study seeks to provide evidence on whether addition of microbiota manipulation by FMT and CDED offers additional benefits when used alongside advance therapies in active CD. The findings from this RCT are expected to significantly enhance treatment strategies, ensuring that patients receive the most effective and appropriate care based on robust scientific evidence. This multi-center double blind placebo-controlled RCT will randomize patients in 1:1:1:1 ratio to FMT, CDED and advance therapy vs sham FMT with advance therapy and CDED vs FMT, Advance therapy and sham diet vs Advance therapy with sham FMT and sham diet for induction and maintenance of remission in patients of active Crohn's disease. Randomization will be held centrally to ensure concealment of allocation. Random numbers will be generated by computerized random number schedule (The RAND), and the randomization list and numbered packing of the intervention will be prepared by a person not involved in the study. Randomization will be performed using permuted blocks of 8. Both the patient and the investigator will be blinded to the intervention

Dysbiosis can be rectified by several methods: antibiotics, prebiotics, probiotics, dietary modulation, and fecal microbiota transplantation. There has been limited success with the isolated use of antibiotics and pre/probiotics in the treatment of IBD. Among the measures of dietary manipulation, the use of exclusive enteral nutrition (EEN) has shown superior, or at least equivalent, efficacy compared with steroids in pediatric CD. Although the results in adults are not as encouraging, recent cohort studies in patients with complicated CD have shown good success rates. Definite exclusion diets that exclude pro-inflammatory dietary constituents have also been tested with good clinical efficacy in patients with CD, who even failed treatment with anti-TNF agents. Various dietary approaches, inclusive of exclusive enteral nutrition, partial enteral nutrition, and Crohn's disease exclusion diet have been reported to be of benefit and are associated with changes in gut microbiome. Fecal microbiota transplantation (FMT) defined as the infusion of fecal suspension from a healthy individual into the gastrointestinal tract of an individual with GI disease carries a diverse population of microbiota and their metabolites and has been tested with varying efficacy in IBD. In general, FMT has shown good success rates in randomized control trials in patients with UC who failed conventional agents. Although limited small RCTs exist in CD, cohort studies have also shown good success rates. Therefore, the use of FMT in addition to standard medical therapy, is a concept that has not been previously explored and forms the basis for the present study. Therefore, a well-powered RCT is required to resolve the role of FMT in CD. In this study, patients will be recruited in four arms. Group A includes FMT+CDED+SMT, in Group B FMT+SMT+SHAM DIET, in Group C Sham FMT+CDED+SMT, in Group D Sham FMT+ Sham Diet+ SMT given. 168 patients will be recruited across 6 centers for around 3 years. Follow-up of the patient will be done at 0,2,6 and 10 weeks and 8 weekly up to 48 weeks.

1. Air quality is a growing concern for health and environment and is one of the modifiable environmental factors. There is growing evidence that a complex interplay of genetic and epigenetic factors like environmental factors, underlies the pathophysiology of ASD. Behavioural issues, sleep habits and cognitive abilities play a significant role in the quality of life of both the affected children and their caregivers 2. Few studies have shown that there is an increased incidence of ASD in children born to mothers exposed to higher levels of air pollution in pregnancy. However, no studies on the effect of air quality on the severity of autism. There are limited studies on the association of air pollution with childhood behaviour and cognitive abilities, especially in neurodevelopmental disorders. No evidence on the impact of air quality on the effectiveness of therapy/standard of care in children with autism, as well as on their sleep habits and behaviour. Our study aims to add to this growing body of evidence of the effect of air pollution on ASD in children.

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by superficial mucosal inflammation. Treatment aims to achieve and maintain remission, improve quality of life, and minimize complications. Advanced therapies, including biologics and small molecules, have significantly improved UC management by targeting specific inflammatory pathways. However, due to the multifactorial nature of UC-driven by genetic, environmental, and microbial factors-many patients do not achieve sustained remission, highlighting a therapeutic ceiling. Gut microbial dysbiosis and immune dysregulation are central to UC pathogenesis, with diet playing a critical role in influencing the gut microbiome. While biologics and small molecules have limitations, innovative approaches like combining fecal microbiota transplantation (FMT) and dietary interventions with advanced therapies show promise. FMT restores microbial balance, modulates immunity, and reduces inflammation, while dietary modifications, such as anti-inflammatory diets, enhance FMT efficacy by creating a favorable environment for donor microbiota engraftment. The present study is designed to evaluate the efficacy of three different microbiome manipulation strategies- FMT, AID and FMT + AID in combination with advanced therapies in patients with active UC in a 2X2 factorial trial design. Patients would be randomized into four different arms: FMT, AID, FMT+AID and placebo. The advanced therapies (biologics or small molecules) would be given in all four arms as standard therapy. With this design the trial would answer two important questions: a) efficacy of combination treatment with advanced therapies and microbiome manipulation strategies in active UC, and b) comparative efficacy of different microbiome manipulation strategies.

The goal of this Interventional Study is to develop and test the Indian Adaptation of Melodic Intonation Therapy (MIT) for Indian patients in with post-stroke Non-Fluent Aphasia (PSNFA). The main question\[s\] it aims to answer are: • To develop the MIT Indian Adaptation tool and check its feasibility • To compare the MIT with standard speech rehabilitation in patient with PSNFA. Participants will undergo Speech Rehabilitation according to the developed module and the standard treatment will be given in the comparator arm. The speech recovery at 12 weeks will be compared in both treatment arms.

The goal of this clinical trial is to study smartphone use restriction as a treatment modality in patients of primary headache. The main question\[s\] it aims to answer are: 1. In patients with primary headache, does restriction of smartphone use lead to reduced consumption of medications (acute, prophylaxis, either or both)? 2. In patients with primary headache, does restriction of smartphone use lead to better responsiveness to medications (acute, prophylaxis, either or both)? 3. Can reduction of smartphone duration be used as a non-pharmacological treatment of primary headache? 4. In patients with primary headache, is the type of smartphone use (phone calls, internet browsing, watching screen) determinant of the severity of headache? 5. Can we make an addiction score to predict which patient should be advised to limit smartphone use based on the above information? 6. In patients with primary headache, does restriction of smartphone use led to improvement in headache severity (frequency, intensity, duration, one of them or all). The smartphone users may further be classified into low and high smartphone users depending upon the smartphone addiction questionnaire (SAQ) (appendix 1) usage score. SUs with 0-1 score on the SAQ were further grouped into low SUs, and patients with score ≥1 were grouped into high SUs. To create a homogenous group, only patients with high SU will be randomized to standard treatment (Arm C) and intervention group (Arm D). Participants will be asked about their smartphone usage, and if found eligible, there will be a run-in period of 4 weeks after which they will be randomized to the intervention (smartphone restriction) or comparison group (no restriction recommended)

Dystonia is a rare syndrome with varying etiologies. Similarly, tremor conditions refractory to medical management and disabling that they need surgical interventions are rare in our setting. So far there are no randomized controlled trials of pallidotomy for management of dystonia. There is scant literature on the long term efficacy and safety of Pallidotomy, thalamotomy and other such lesioning procedures in the management of movement disorders. The current literature is significantly plagued by publication bias as case reports with successful outcomes are likely to be selectively published in journals or conference abstracts. Lesioning procedures though seem to be effective are often considered to be risky, especially bilateral pallidotomy is not preferred by several centres. However, our center routinely performs simultaneous bilateral pallidotomy. To generate long term data on the efficacy and safety of lesioning procedures in rare diseases like dystonias especially the effect of functional neurosurgery on varying etiologies of the disease, robust registries are required which collect data on all consecutive patients who undergo the procedure.

Currently, no literature is available regarding degree of cortical excitability and its correlation with various epileptic syndromes and disorders such as West Syndrome in pediatric age group. Studying the complex interaction of cortical excitability, seizures, neurobehavioral patterns and brain maturation in children may provide valuable information and new insights about the underlying neuropathogenic pathways in childhood epilepsy. West Syndrome is a unique epilepsy syndrome amalgamating infantile onset epilepsy with significant neurodevelopmental delay. Due to this reason, it is the ideal disorder to study this complex interaction. How cortical excitability correlates with disease activity in West Syndrome is speculative. The ability of disease characteristics such as degree of cortical excitability to predict successful outcome after ACTH therapy (non-invasive biomarker of treatment response) in children with West Syndrome has not been explored. Most importantly, the present study may be a hypothesis generating initial step bringing new insights into neurocognitive effects of seizures, seizure pathogenesis, individualized antiepileptic drug therapy and for studying treatment response. The investigators aim to determine the change in cortical excitability pre and post ACTH therapy, in children with West syndrome and whether the change predicts responsiveness to ACTH therapy, in terms of reduction in spasm frequency at 12 weeks.

The goal of this clinical trial\] is to compare cervical collar versus neck stabilization surgery in diagnosed patients of Hirayama disease who have been reporting worsening of problems in the past six months. The main question\[s\] it aims to answer are: • Is cervical stabilization surgery (Posterior cervical fixation) superior to conservative management in the form of cervical collar placement in patients with progressive Hirayama disease, observed at six months after intervention Participants will have equal chance to: * Undergo cervical fixation surgery * Cervical collar management The investigators will study and compare the efficacy of both treatments upto six months after intervention

Generalized dystonia is treated with pallidotomy. This is based on observational data which is significantly limited by publication bias and there are no RCTs. The case reports focus on successful outcomes and case series have an inherent selection bias. Bilateral pallidotomy has been used in our institute in a series of patients with generalized and segmental dystonia and have been seen to show good efficacy. However, the existing literature suggests that it is also associated with dysphagia and dysarthria in some cases and thus simultaneous bilateral pallidotomy is not preferred in several centres. However, our center routinely performs simultaneous bilateral pallidotomy. The response rates and compliations of the procedure have not been systematically studied in RCT and we need to generate data on the efficacy and safety of Pallidotomy on generalized and segmental dystonia. This randomized controlled trial will fill the void in knowledge in this field.