DIAGNODE-1: First intralymphatic GAD-alum dosing study
What this study tests
Open-label pilot of intralymphatic GAD-alum plus vitamin D in 12 people with recent-onset T1D. It reported tolerability, immune responses and apparent C-peptide preservation, but the uncontrolled design cannot establish treatment efficacy or uncommon harms.
Editorial review: .
Registry checked: 2026-09-17. Registry’s own update: 2020-04-27.
Most recent recorded citation date: 2018-05-24. Only explicit date metadata is included; an undated citation may be newer. This does not mean every claim was reviewed on that date.
Trial status, labels and access can change between reviews. How we review the evidence · How to read the evidence
Evidence at a glance
- Who can enter the study?
- Recent-onset type 1 diabetes (diagnosed within 6 months) with some remaining insulin production (fasting C-peptide >=0.12 nmol/L) and positive GAD autoantibodies. Diagnosed between ages 12 and 30; not on immunosuppressants or non-insulin diabetes drugs. Registered eligibility ↗Enrollment criteria describe who may enter. They do not establish who was analyzed or the denominator for a reported result.
- Reported benefit and results
- No serious adverse events occurred; injection-site reactions were minimal (only mild tenderness in 1-2 participants). The lymph-node route induced a strong antigen-specific immune response (GAD antibodies far higher than older subcutaneous dosing, a Th2-skewed cytokine profile dominated by IL-13, a shift in IgG subclasses, and reduced T-cell proliferation). Insulin-producing capacity (C-peptide) appeared preserved at 6 and 15 months, with 11 of 12 reaching partial remission at 15 months; in longer follow-up, 8 of 12 were classified as "good responders."Read the result sources and their limitations →
- Important harms
- Read the reported results, safety discussion and original sources. A separate harms summary is not available; this does not establish safety.
- Research access and approval
- Study regions: European Union. A trial listing does not establish product approval or current recruitment at a particular site. Check the study’s current entry requirements.
- What remains uncertain?
- Read the full discussion and original sources for study limitations. Planned endpoints and completion dates are not results.
Research status alone does not establish approval, clinical benefit or local availability.
Primary endpoints
- Safety: injection-site reactions (erythema, edema, hematoma, tenderness, pain, itching) at months 1, 2, 3 and 32
The full picture
What was tested, and why it matters
Type 1 diabetes happens because the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. One protein the immune system targets is GAD65. For years, researchers have tried to "retrain" the immune system by giving GAD65 as a kind of therapeutic vaccine (called GAD-alum, or Diamyd), but injecting it under the skin produced only modest effects.1
DIAGNODE-1 tested a smarter delivery route: injecting a tiny dose of GAD-alum directly into a lymph node — the place where immune responses are actually coordinated — guided by ultrasound.2 The hope was that this would generate a stronger, more protective (tolerance-promoting) immune response using far less drug.
Who it was for, and how it was designed
This was a small open-label pilot trial (no placebo group) run in Linköping, Sweden, enrolling 12 people with recently diagnosed type 1 diabetes (within 6 months) who still made some of their own insulin.2 Participants were diagnosed between ages 12 and 30 and carried GAD autoantibodies.2 Each received 4 µg of GAD-alum injected into a groin lymph node on three occasions, one month apart, plus daily oral vitamin D as an immune-supporting add-on.2 The main goal was simply to check safety; the team also tracked immune markers and insulin production for years afterward.2
Key results
The approach was safe and well tolerated. There were no serious adverse events, and injection-site reactions were minimal — only mild tenderness in one or two participants.2
Despite using a much smaller dose, the lymph-node route triggered a stronger and qualitatively different immune response than older under-the-skin dosing: GAD antibody levels rose far higher, the cytokine profile shifted toward a calmer, Th2-type pattern dominated by IL-13, antibody subclasses shifted (less IgG1, more IgG2/IgG3/IgG4), and GAD-specific T-cell proliferation went down — all consistent with steering the immune system away from attack.1
Encouragingly, insulin-producing capacity (C-peptide) appeared preserved at 6 and 15 months, and 11 of 12 participants reached partial remission by 15 months.3 In longer follow-up, 8 of 12 were classified as "good responders," and a genetic subgroup (carrying the HLA DR3-DQ2 type) seemed to respond best.3
What it means and what's next
DIAGNODE-1 was the proof-of-concept that made lymph-node GAD-alum worth pursuing. Because there was no placebo group, it could not prove the treatment slows diabetes on its own — but its safety and immune signals directly justified the larger, randomized, placebo-controlled DIAGNODE-2 trial.3
Sources
- [1]Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes. · Peer-reviewed study · 2018-05-24
Tavira B, Barcenilla H, Wahlberg J, Achenbach P, Ludvigsson J, Casas R. Intralymphatic Glutamic Acid Decarboxylase-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients: A Pilot Clinical Trial in Type 1 Diabetes. Journal of Diabetes Research (2018).
Tavira B, et al. Intralymphatic GAD-Alum Administration Induced Th2-Like-Specific Immunomodulation in Responder Patients. Journal of Diabetes Research (2018).
- [2]ClinicalTrials.gov. Open Label Pilot Trial in Adults With Recent-onset T1D to Evaluate the Safety, Diabetes Status and Immune Response of GAD-antigen (Diamyd) Therapy Administered Into Lymph Nodes (DIAGNODE), NCT02352974. *ClinicalTrials.gov* (2020) · Trial registry
ClinicalTrials.gov. Open Label Pilot Trial in Adults With Recent-onset T1D to Evaluate the Safety, Diabetes Status and Immune Response of GAD-antigen (Diamyd) Therapy Administered Into Lymph Nodes (DIAGNODE), NCT02352974. ClinicalTrials.gov (2020).
ClinicalTrials.gov. NCT02352974 — study design, eligibility, intervention and dosing schedule. ClinicalTrials.gov (2020).
ClinicalTrials.gov. NCT02352974 — posted results: adverse events (0 serious events in 12 participants) and injection-site reaction outcomes. ClinicalTrials.gov (2020).
- [3]Ludvigsson J, et al. Intra-lymphatic administration of GAD-alum in type 1 diabetes: long-term follow-up and effect of a late booster dose (the DIAGNODE Extension trial). *Diabetologia / PMC* (2022) · Peer-reviewed study
Ludvigsson J, et al. Intra-lymphatic administration of GAD-alum in type 1 diabetes: long-term follow-up and effect of a late booster dose (the DIAGNODE Extension trial). Diabetologia / PMC (2022).
Ludvigsson J, et al. DIAGNODE Extension trial — responder analysis, HLA DR3-DQ2 subgroup, and late booster dose. PMC (2022).