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Schizophrenia DisorderPhase 3NCT07770282

Efficacy and Safety of Semaglutide Versus Placebo on Cardiometabolic Profile in Patients With Schizophrenia With Metabolic Syndrome

A Phase 3 study testing Semaglutide + TAU in people with Schizophrenia Disorder and Metabolic Syndrome, run by All India Institute of Medical Sciences, Bhubaneswar.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

Patients with schizophrenia on second-generation antipsychotics have a high burden of metabolic syndrome and elevated cardiovascular risk, with few effective treatment options. This multicentre, double-blind, placebo-controlled randomised trial evaluates whether adjunctive oral semaglutide 3 mg once daily, added to… Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
What is being tested?
Semaglutide + TAU
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
600 participants
Where
No sites listed yet
Study dates
1 Dec 2026to 30 Dec 2030
Phase
Phase 3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Clinically diagnosed schizophrenia (ICD-11) on a second-generation antipsychotic (SGA) for more than 6 months.
  • Metabolic syndrome per NCEP ATP III definition.
  • Aged above 25 years, any gender.
  • Patient / Legally Authorised Representative (LAR) provides voluntary written informed consent.

Who cannot join

  • ● On clozapine, aripiprazole, or a combination of SGAs.
  • Any contraindication to semaglutide.
  • Comorbid severe psychiatric, medical or neurological disorder.
  • History of organicity or significant head injury.
  • Pregnant or breastfeeding.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Debadatta Mohapatra, MD contact

+91 9437658251

psych_debadatta@aiimsbhubaneswar.edu.in

About this study

Official title: Efficacy and Safety of Semaglutide Versus Placebo on Cardiometabolic Profile in Patients With Schizophrenia With Metabolic Syndrome: A Multicentre, Double-Blind, Randomised Controlled Trial (ESCaMS Trial)

Patients with schizophrenia on second-generation antipsychotics have a high burden of metabolic syndrome and elevated cardiovascular risk, with few effective treatment options. This multicentre, double-blind, placebo-controlled randomised trial evaluates whether adjunctive oral semaglutide 3 mg once daily, added to treatment as usual, reduces 10-year cardiovascular risk (QRISK3) and improves insulin resistance, lipids, weight and metabolic biomarkers over 24 weeks compared with placebo, while confirming psychiatric safety and tolerability.

Read the detailed description

Schizophrenia affects approximately 0.3-1.4% of the Indian population and is associated with a life expectancy reduced by up to 20 years, largely due to cardiovascular disease. Roughly one in three patients has metabolic syndrome, a risk substantially increased by second-generation antipsychotics (SGAs). Existing pharmacological options (metformin, topiramate, aripiprazole) offer only modest to minimal benefit, and major GLP-1 receptor agonist trials have excluded people with severe mental illness.

This is a multicentre, two-arm, parallel-group, double-blind, placebo-controlled randomised controlled trial. 600 clinically stable adults with schizophrenia (ICD-11) and metabolic syndrome (NCEP ATP III), on an SGA for over six months, will be randomised 1:1 to adjunctive oral semaglutide 3 mg once daily or matching placebo, both added to treatment as usual (TAU). Dosing is titrated from a low starting dose to 3 mg/day. Central computer-generated block randomisation stratified by centre is used, with allocation concealment by sequentially numbered opaque sealed envelopes (SNOSE). Assessments occur at baseline, 12 weeks and 24 weeks, with weekly telephonic safety follow-up. The primary endpoint is change in QRISK3 at 24 weeks.

Being tested
Semaglutide + TAU, Placebo + TAU
Keywords
Semaglutide, Metabolic syndrome, QRISK3, Cardiometabolic risk, Schizophrenia
Medical subject headings
Schizophrenia, Metabolic Syndrome, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Semaglutide + TAUDrug

    Semaglutide - oral tablet 3 mg once daily in the morning (titrated up from a low starting dose over 5 days), added to ongoing second-generation antipsychotic (TAU), for 24 weeks.

  • Placebo + TAUDrug

    Placebo - matching oral tablet once daily in the morning, added to ongoing second-generation antipsychotic (TAU), for 24 weeks

Study groups in NCT07770282
Study groupRoleWhat they receive
SemaglutideExperimentalDrug: Semaglutide - oral tablet 3 mg once daily in the morning (titrated up from a low starting dose over 5 days), added to ongoing second-generation antipsychotic (TAU), for 24 weeks.
Receives: Drug: Semaglutide + TAU
PlaceboPlacebo comparatorDrug: Placebo - matching oral tablet once daily in the morning, added to ongoing second-generation antipsychotic (TAU), for 24 weeks.
Receives: Drug: Placebo + TAU

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in QRISK3 (QResearch Cardiovascular Risk Prediction Algorithm Version 3),10-year cardiovascular risk score

    QRISK3 is a cardiovascular risk prediction tool that calculates the 10-year absolute risk of developing cardiovascular disease (heart attack or stroke). The scale produces a percentage score ranging from 0% to 100%, where 0% represents minimum cardiovascular risk and 100% represents maximum theoretical risk. Risk stratification is typically classified as: <5% = low risk, 5-10% = intermediate risk, 10-20% = high risk, and >20% = very high risk. A score of >20% (or approaching 100%) represents the worst clinical situation, indicating substantially elevated 10-year cardiovascular disease risk requiring intensive preventive interventions, including lifestyle modification and pharmacological treatment (statins, antihypertensives). QRISK3 incorporates clinical variables (age, blood pressure, cholesterol), demographic factors, and comorbidities to stratify risk and guide evidence-based prevention strategies in primary care settings.

    Measured: Baseline to Week 24

Secondary outcomes (9)

  1. Change in LDL/HDL ratio

    Change from baseline in lipid ratio from fasting lipid profile

    Measured: Baseline, Week 12, Week 24

  2. Change in insulin resistance (HOMA-IR)

    Change in HOMA-IR from fasting glucose and serum insulin

    Measured: Baseline to Week 24

  3. Change in high-sensitivity CRP (hs-CRP)

    Change in hs-CRP measured by ELISA

    Measured: Baseline to Week 24

  4. Change Waist circumference

    Anthropometric change from baseline

    Measured: Baseline, Week 12, Week 24

  5. Change in Leptin/Adiponectin ratio

    Change in metabolic biomarker measured by ELISA

    Measured: Baseline, Week 24

  6. Change in PANSS score

    Change in Positive and Negative Syndrome Scale (psychiatric safety), The assessment instrument employs a standardized scoring mechanism with a theoretical range spanning from a minimum of 30 to a maximum of 210 points. This metric demonstrates an inverse relationship between numerical score and outcome favorability; therefore, higher scores are indicative of more severe or unfavorable conditions, whereas lower scores denote relatively improved or more favorable circumstances. Consequently, respondents achieving scores proximate to the minimum threshold (30) represent optimal outcomes, while those obtaining scores approaching the maximum threshold (210) signify substantially compromised or critical situations requiring immediate clinical or interventional consideration.

    Measured: Baseline, Week 12, Week 24

  7. Change in CGI-SCH score

    The CGI-SCH is a clinician-rated assessment scale measuring overall severity of schizophrenia symptoms. The scale ranges from 1 to 7, where 1 represents "normal, not at all ill" (minimum score) and 7 represents "among the most extremely ill" (maximum score). Scores are interpreted as: 1-2 = normal to borderline, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = most extremely ill. A score of 7 indicates the worst clinical situation, reflecting severe and pervasive psychotic symptoms with significant functional impairment. The CGI-SCH is widely used in clinical trials and practice to track global severity and treatment response in schizophrenia over time.

    Measured: Baseline, Week 12, Week 24

  8. Change in WHO QOL-BREF

    The WHO QOL-BREF is a 26-item self-report instrument measuring overall quality of life across four domains: Physical Health, Psychological Health, Social Relationships, and Environment. Each item is rated on a 1-5 scale, yielding a minimum total score of 26 (poorest quality of life) and a maximum total score of 130 (best quality of life). Unlike severity scales, higher scores indicate better quality of life, while lower scores indicate poorer quality of life. A score of 26 represents the worst clinical situation, reflecting severely compromised physical health, psychological distress, social isolation, and inadequate environmental resources. Domain scores range from 4-20 each and can be analyzed separately to identify specific areas of impairment. The WHO QOL-BREF is widely used in clinical practice and research to evaluate functional quality of life, treatment outcomes, and overall well-being in various populations.

    Measured: Baseline, Week 12, Week 24

  9. Treatment-emergent adverse events (TEAE)

    Frequency and severity of TEAEs; safety and tolerability

    Measured: Continuous, weekly to Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Aug 2026
  2. Study start1 Dec 2026 (estimated)
  3. Primary completion30 Jul 2030 (estimated)
  4. Study completion30 Dec 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
600 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07770282
Sponsor's protocol ID
EMF/Psych/2026-27/35
Status last verified
Aug 2026
First submitted
10 Aug 2026
Last updated
18 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: dataset access restricted to the PI and authorised research team; sharing per ICMR and institutional polic

Publications

  • Bak M, Fransen A, Janssen J, van Os J, Drukker M. Almost all antipsychotics result in weight gain: a meta-analysis. PLoS One. 2014 Apr 24;9(4):e94112. doi: 10.1371/journal.pone.0094112. eCollection 2014.

    PubMed 24763306

  • Allison DB, Mentore JL, Heo M, Chandler LP, Cappelleri JC, Infante MC, Weiden PJ. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999 Nov;156(11):1686-96. doi: 10.1176/ajp.156.11.1686.

    PubMed 10553730

  • Walss-Bass C, Weintraub ST, Hatch J, Mintz J, Chaudhuri AR. Clozapine causes oxidation of proteins involved in energy metabolism: a possible mechanism for antipsychotic-induced metabolic alterations. Int J Neuropsychopharmacol. 2008 Dec;11(8):1097-104. doi: 10.1017/S1461145708008882. Epub 2008 May 9.

    PubMed 18466668

  • Rummel-Kluge C, Komossa K, Schwarz S, Hunger H, Schmid F, Lobos CA, Kissling W, Davis JM, Leucht S. Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: a systematic review and meta-analysis. Schizophr Res. 2010 Nov;123(2-3):225-33. doi: 10.1016/j.schres.2010.07.012. Epub 2010 Aug 7.

    PubMed 20692814

  • Mitchell AJ, Vancampfort D, Sweers K, van Winkel R, Yu W, De Hert M. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders--a systematic review and meta-analysis. Schizophr Bull. 2013 Mar;39(2):306-18. doi: 10.1093/schbul/sbr148. Epub 2011 Dec 29.

    PubMed 22207632

  • Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry. 2007 Oct;64(10):1123-31. doi: 10.1001/archpsyc.64.10.1123.

    PubMed 17909124

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Semaglutide + TAU in people with Schizophrenia Disorder and Metabolic Syndrome, run by All India Institute of Medical Sciences, Bhubaneswar.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 18 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Debadatta Mohapatra, MD (+91 9437658251, psych_debadatta@aiimsbhubaneswar.edu.in), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in QRISK3 (QResearch Cardiovascular Risk Prediction Algorithm Version 3),10-year cardiovascular risk score (time frame: Baseline to Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07770282, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2026; AzTrials last refreshed its copy on 8 Nov 2026.

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