SHIELD-T1D: Shingrix and GLP-1 Agonist for Beta-Cell Preservation in Recent-Onset Type 1 Diabetes.

NCT07614412 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: shingrix-Glp1-type1 diabetes
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive destruction of pancreatic beta cells mediated by autoreactive T lymphocytes, resulting in absolute insulin deficiency. Preservation of residual beta-cell function at the time of diagnosis is a critical therapeutic window, as even marginal endogenous insulin secretion - reflected by detectable C-peptide levels - is associated with improved glycemic control, reduced hypoglycemia burden, and decreased long-term vascular complication rates. This study evaluates the hypothesis that combinatorial immunomodulation - using the AS01B adjuvant system within the Recombinant Zoster Vaccine (RZV; Shingrix, GSK) alongside metabolic and cytoprotective support via a GLP-1 receptor agonist (semaglutide) - can synergistically preserve residual beta-cell function in adults within 100 days of T1D diagnosis. The AS01B adjuvant system activates innate immune pathways that promote regulatory T-cell (Treg) expansion and shift the immunological milieu toward tolerance, while GLP-1 receptor agonism provides direct beta-cell cytoprotection, reduces glucotoxicity, and may suppress autoimmune cytokine signaling. SHIELD-T1D is a randomized, double-blind, placebo-controlled, parallel-group Phase II clinical trial enrolling 240 adults (18-50 years) diagnosed with T1D within 100 days, with confirmed residual beta-cell function (stimulated C-peptide ≥0.2 nmol/L). Participants are randomized 1:1:1:1 to one of four arms: (1) Shingrix alone, (2) Semaglutide alone, (3) Shingrix + Semaglutide combination, or (4) dual placebo. The primary endpoint is change in 2-hour stimulated C-peptide AUC during a Mixed Meal Tolerance Test (MMTT) from baseline to 12 months. This phase II randomized, double-blind, placebo-controlled multicenter trial will evaluate the efficacy and safety of the recombinant zoster vaccine (Shingrix) and a glucagon-like peptide-1 (GLP-1) receptor agonist, alone and in combination, for preservation of residual beta-cell function in adults with recent-onset type 1 diabetes. The working hypothesis is that combining AS01 adjuvant-mediated immunomodulation with the metabolic and cytoprotective actions of a GLP-1 receptor agonist will provide dual protection for pancreatic beta cells, slowing autoimmune destruction and improving functional insulin secretion compared with placebo.

Conditions

Type 1 Diabetes Mellitus

Keywords

Type 1 Diabetes; Beta-cell preservation; C-peptide; GLP-1 receptor agonist; Recombinant zoster vaccine; Shingrix; AS01 adjuvant; Immunomodulation; Autoimmunity

Outcome Measures

Primary Outcomes (1)

• Change in 2-hour stimulated C-peptide Area Under the Curve (AUC) during a Mixed Meal Tolerance Test (MMTT)

  The primary efficacy endpoint is the change in the 2-hour stimulated C-peptide AUC (measured in nmol/L/min) from baseline to 12 months, assessed via a standardized 2-hour MMTT. This measures the capacity of residual pancreatic beta cells to secrete insulin in response to a physiological stimulus.

  Baseline and 12 months

Secondary Outcomes (1)

• Glycated Hemoglobin (HbA1c) levels

  Baseline, 12 months, and 24 months

Study Arms (4)

Shingrix + Semaglutide Placebo

ACTIVE COMPARATOR

RZV 0.5 mL IM at Months 0 and 2 + subcutaneous saline placebo once weekly for 24 months. Standard-of-care insulin therapy continues throughout

Drug: Recombinant Zoster Vaccine (Shingrix; RZV); Drug: Semaglutide (Ozempic®); Drug: Placebo (saline injection)

Semaglutide + RZV Placebo

ACTIVE COMPARATOR

Semaglutide 0.25 mg SC weekly for 4 weeks, then 0.5 mg SC weekly for 24 months + IM saline placebo at Months 0 and 2. Standard-of-care insulin throughout.

Drug: Recombinant Zoster Vaccine (Shingrix; RZV); Drug: Semaglutide (Ozempic®); Drug: Placebo (saline injection)

Shingrix + Semaglutide (Combination

EXPERIMENTAL

RZV 0.5 mL IM at Months 0 and 2 + Semaglutide 0.25 mg SC weekly (escalating to 0.5 mg) for 24 months. Standard-of-care insulin throughout. PRIMARY EXPERIMENTAL ARM.

Drug: Recombinant Zoster Vaccine (Shingrix; RZV); Drug: Semaglutide (Ozempic®); Drug: Placebo (saline injection)

Double placebo

PLACEBO COMPARATOR

IM saline placebo at Months 0 and 2 + subcutaneous saline placebo once weekly for 24 months. Standard-of-care insulin throughout

Drug: Recombinant Zoster Vaccine (Shingrix; RZV); Drug: Semaglutide (Ozempic®); Drug: Placebo (saline injection)

Interventions

Semaglutide (Ozempic®) DRUG

Drug: Semaglutide - GLP-1 receptor agonist (acylated GLP-1 analogue with 94% sequence homology to native GLP-1). Dose Escalation: 0.25 mg SC once weekly (Weeks 1-4) → 0.5 mg SC once weekly (Weeks 5-24 months). Route: Subcutaneous injection (abdomen, thigh, or upper arm; rotate sites). Manufacturer: Novo Nordisk. FDA Status: Approved for T2D; investigational use in T1D (IND required). Mechanism of Action: GLP-1 receptor agonism enhances glucose-dependent insulin secretion, inhibits glucagon, promotes beta-cell survival and proliferation, reduces ER stress, and suppresses pro-inflammatory cytokine-mediated apoptosis (IL-1β, IFN-γ, TNF-α).

Double placebo; Semaglutide + RZV Placebo; Shingrix + Semaglutide (Combination; Shingrix + Semaglutide Placebo

Placebo (saline injection) DRUG

Saline placebo administered as intramuscular injection (matching RZV volume 0.5 mL) at Months 0 and 2, and/or as subcutaneous injection (matching semaglutide volume) once weekly for 24 months. Used in control and single-active arms to maintain blinding.

Double placebo; Semaglutide + RZV Placebo; Shingrix + Semaglutide (Combination; Shingrix + Semaglutide Placebo

Recombinant Zoster Vaccine (Shingrix; RZV) DRUG

Intervention 1: Recombinant Zoster Vaccine (Shingrix; RZV) Drug/Biological: Recombinant zoster vaccine (lyophilized VZV glycoprotein E antigen 50 μg + AS01B adjuvant system \[MPL 50 μg + QS-21 50 μg in liposomal formulation\]). Dose: 0.5 mL intramuscular injection (reconstituted per manufacturer's instructions). Schedule: Two doses - Month 0 and Month 2 (8-week interval). Route: Intramuscular (deltoid, non-dominant arm preferred). Manufacturer: GlaxoSmithKline (GSK). FDA Status: Approved for herpes zoster prevention; use in T1D is investigational (IND required). Mechanism of Action: AS01B adjuvant promotes DC maturation, Th1 polarization, and regulatory T-cell induction via TLR4 (MPL) and saponin (QS-21) pathways

Double placebo; Semaglutide + RZV Placebo; Shingrix + Semaglutide (Combination; Shingrix + Semaglutide Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of Type 1 Diabetes (T1D) according to American Diabetes Association (ADA) criteria.
• Age 18 to 50 years (inclusive) at the time of screening.
• Randomization within 100 days of the first insulin injection.
• Confirmed residual beta-cell function, defined as a peak stimulated C-peptide level ≥0.2 nmol/L during a Mixed Meal Tolerance Test (MMTT) performed at screening.
• Presence of at least one T1D-related autoantibody (GADA, IA-2A, ZnT8A, or ICA).
• Willingness to comply with intensive insulin therapy and glucose monitoring.
• Females of childbearing potential must have a negative pregnancy test and agree to use highly effective contraception.

You may not qualify if:

• History of diabetic ketoacidosis (DKA) within 4 weeks of screening.
• Prior use of any immunotherapy or investigational agents for T1D.
• Current or prior use of GLP-1 receptor agonists, DPP-4 inhibitors, or SGLT2 inhibitors.
• History of pancreatitis or medullary thyroid carcinoma.
• Active or chronic infection (e.g., HIV, Hepatitis B or C, Tuberculosis).
• Pregnancy or breastfeeding.
• Significant renal, hepatic, or cardiovascular disease.
• History of severe allergic reaction to any component of the Recombinant Zoster Vaccine (Shingrix) or semaglutide.
• Current use of systemic corticosteroids or other immunosuppressive medications.

Sponsors & Collaborators

• Ministry of Health, Saudi Arabia: lead

Study Sites (1)

Ministry of Health Medical City

Riyadh, Saudi Arabia

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Autoimmune Diseases

Interventions

semaglutide; Sodium Chloride

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Amr Ahmed, MD, PhD

  Ministry of Health, Saudi Arabia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Placebo injections will be identical in volume, appearance, and administration route. Randomization codes will be held by an independent unblinded pharmacist. Emergency unblinding procedures are available via a 24-hour DSMB-approved unblinding protocol
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ministry of heath, public health department, saudia arabia

Study Record Dates

• First Submitted: May 16, 2026
• First Posted: May 29, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: May 29, 2026

Record last verified: 2026-05

Locations

SA (1)