## Protocol Section
### Identification Module
**NCT ID:** NCT04262479

**Acronym:** GADinLADA

**Brief Title:** Injections of Glutamic Acid Decarboxylase (GAD) for LADA Type of Diabetes

**Official Title:** A Pilot Study on Safety, Feasibility and Insulin-promotion by Intra-inguinal Lymph Node Injections of Glutamic Acid Decarboxylase (GAD) in Patients With LADA Type of Diabetes

#### Organization Study ID Info
**ID:** GADinLADA
#### Organization
**Class:** OTHER
**Full Name:** Norwegian University of Science and Technology
#### Secondary ID Infos
**ID:** 2019-002692-34
**Type:** EUDRACT_NUMBER
### Status Module
#### Completion Date
**Date:** 2022-05-05

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-05-26

**Type:** ACTUAL

**Last Update Submit Date:** 2022-05-25

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2022-05-05

**Type:** ACTUAL

#### Start Date
**Date:** 2020-03-02

**Type:** ACTUAL

**Status Verified Date:** 2022-05

#### Study First Post Date
**Date:** 2020-02-10
**Type:** ACTUAL
**Study First Submit Date:** 2020-02-05
**Study First Submit QC Date:** 2020-02-06
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** St. Olavs Hospital

**Class:** INDUSTRY

**Name:** Diamyd Medical AB

**Class:** OTHER

**Name:** Karolinska Institutet

**Class:** OTHER_GOV

**Name:** Linkoeping University

#### Lead Sponsor

**Class:** OTHER

**Name:** Norwegian University of Science and Technology

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This study will evaluate the effects of 3 intra-nodal injections of GAD-alum (Diamyd), together with oral vitamin D supplementation. Safety and feasibility of the treatment will be evaluated and also effects on the immune system and on the preservation of endogenous insulin production.

### Conditions Module

**Conditions:**

- Latent Autoimmune Diabetes in Adults

**Keywords:**

- Glutamic Acid Decarboxylase

- Alum Compounds

- Injections

- Inguinal Canal

- Diamyd

- rhGAD65

- Vitamin D

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 14

**Type:** ACTUAL

**Phases:**

- PHASE2

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Each study participant will receive 3 injections of 4 µg GAD-alum (Diamyd). The first, second and third injection will be one month apart.

Vitamin D (Divisun 2000 IE) will be given from one month before the first injection of GAD-alum until one month after the third injection (120 days in total).

**Intervention Names:**

- Drug: recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel

- Drug: Vitamin D

**Label:** GAD-vaccination with vitamin D suppletion

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- GAD-vaccination with vitamin D suppletion

**Description:** 3 intra-inguinal injections (into the lymph nodes) of GAD-alum one month apart. Supplier Diamyd Medical AB in Stockholm, Sweden

**Name:** recombinant human glutamic acid dehydrogenase (rhGAD65), formulated in aluminium hydrogel

**Other Names:**

- GAD-alum (Diamyd(R))

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- GAD-vaccination with vitamin D suppletion

**Description:** 1 tablet/day, total daily dose of 2000 IE given per os from day -30 through day 90. Supplier Meda, Solna, Sweden

**Name:** Vitamin D

**Other Names:**

- Divisun 2000 IE

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** skin reactions 1 hour post injection vs. before injection

**Measure:** injection site skin reactions

**Time Frame:** 1 hour

**Description:** continuously monitored and registered

**Measure:** Occurrence of adverse events (AEs)

**Time Frame:** summarized at 5 months

**Description:** continuously monitored and registered

**Measure:** Occurrence of adverse events (AEs)

**Time Frame:** summarized at 12 months

**Description:** concentration in serum after the first injection vs baseline

**Measure:** GAD65A titer in serum

**Time Frame:** at 5 months

**Description:** concentration in serum after the first injection vs baseline

**Measure:** GAD65A titer in serum

**Time Frame:** at 12 months

#### Secondary Outcomes

**Description:** measured by glucagon- and MMTT stimulated C-peptide

**Measure:** Insulin secretion

**Time Frame:** 5 months after first injection

**Description:** measured by glucagon- and MMTT stimulated C-peptide

**Measure:** insulin secretion

**Time Frame:** 12 months after first injection

**Measure:** Change in HbA1c

**Time Frame:** from baseline to 5 and 12 months after the first injection

**Measure:** Change in fasting glucose

**Time Frame:** from baseline to 5 and 12 months after the first injection

**Measure:** Change in Fasting C-peptide

**Time Frame:** between baseline and 5 and 12 months after the first injection

**Measure:** Change in maximum C-peptide during Mixed Meal Tolerance Test (MMTT)

**Time Frame:** between baseline and 5 and 12 months after the first injection

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Signed informed consent by the patient.
2. Diagnosis of LADA and diabetes debut within the last 18 months before inclusion. LADA should be defined by the criteria of age ≥30 years at the onset of diabetes, anti-GAD positivity and no clinical need for permanent insulin treatment during the first 3 months after the diagnosis of diabetes.
3. Fasting C-peptid levels ≥ 0.3 nmol/l
4. High GADA titers (\>190 U/ml)
5. Patients must be insulin independent at baseline by clinical judgement and C-peptide criteria
6. Antidiabetic medication in the form of metformin is acceptable for inclusion as well as medications not mentioned under exclusion criteria
7. Females must agree to avoid pregnancy, and must have a negative urine pregnancy test.

Patients of childbearing potential must agree to use adequate contraception, until one (1) year after the last administration of GAD-alum. Adequate contraception is as follows:

For females of childbearing potential:

1. oral (except low-dose gestagen (lynestrenol and norestisteron)), injectable, or implanted hormonal contraceptives
2. combined (estrogen and progestogen containing)
3. oral, intravaginal or transdermal progesterone hormonal contraception associated with inhibition of ovulation
4. intrauterine device
5. intrauterine hormone-releasing system (for example, progestin-releasing coil)
6. bilateral tubal occlusion
7. vasectomized male (with appropriate post vasectomy documentation of the absence of sperm in the ejaculate)
8. male partner using condom
9. abstinence from heterosexual intercourse

For males of childbearing potential:

1. condom (male)
2. abstinence from heterosexual intercourse

Exclusion Criteria:

1. Current or previous treatment with immunosuppressant therapy (topical or inhaled steroids are accepted)
2. Continuous treatment with anti-inflammatory drug (sporadic treatment e.g. because of headache or in connection with fever a few days will be accepted)
3. Systemic treatment with glucocorticoids
4. Treatment with any vaccine, including influenza vaccine, within 1 month prior to planned first study drug dose or planned treatment with any vaccine up to 1 month after the last injection with study drug
5. Antidiabetic medication (metformin excepted)
6. Significantly abnormal hematology results at screening (i.e. anemia with hemoglobin \< 12 g/L).
7. A history of epilepsy, head trauma or cerebrovascular accident, or clinical features of continuous motor unit activity in proximal muscles
8. Clinically significant history of acute reaction to vaccines in the past.
9. Renal disease (as defined by serum creatinine \>150 µmol/l)
10. Serious cardiovascular events (myocardial infarction, stroke) within the last year preceding recruitment.
11. Participation in other clinical trials with a new chemical entity within the previous 3 months
12. A history of alcohol or drug abuse
13. Known HIV or hepatitis
14. Presence of associated serious disease or condition, including active skin infections that preclude intralymphatic injection, which in the opinion of the investigator makes the patient non-eligible for the study
15. Other serious chronic disease as judged by investigator.
16. Females who are lactating, are pregnant or intend to become pregnant.
17. Inability or unwillingness to comply with the provisions of this protocol
18. Deemed by the investigator not being able to follow instructions and/or follow the study protocol
19. Treatment any other supplementation of with vitamin D, marketed or not, or unwilling to abstain from such medication during the trial 120 days daily intake of Divisun (non-investigational medicinal product)

**Maximum Age:** 70 Years

**Minimum Age:** 30 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Trondheim

**Country:** Norway

**Facility:** Department of Endocrinology, St Olavs Hospital

**Location 2:**

**City:** Stockholm

**Country:** Sweden

**Facility:** Akademiskt Specialistcentrum, Centrum for Diabetes, and Karolinska Institute

#### Overall Officials

**Official 1:**

**Affiliation:** St Olavs Hospital, Medisinsk Klinikk

**Name:** Anne Hildur Henriksen, MD PhD

**Role:** STUDY_DIRECTOR

**Official 2:**

**Affiliation:** Norwegian University of Science and Technology, IKOM

**Name:** Torstein Baade Rø, MD

**Role:** STUDY_DIRECTOR

### IPD Sharing Statement Module

**Description:** There is not a plan to make IPD available.

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Hals IK, Fiskvik Fleiner H, Reimers N, Astor MC, Filipsson K, Ma Z, Grill V, Bjorklund A. Investigating optimal beta-cell-preserving treatment in latent autoimmune diabetes in adults: Results from a 21-month randomized trial. Diabetes Obes Metab. 2019 Oct;21(10):2219-2227. doi: 10.1111/dom.13797. Epub 2019 Jun 19.

**PMID:** 31148332

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000044882

- Term: Glucose Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000004700

- Term: Endocrine System Diseases

- ID: D000001327

- Term: Autoimmune Diseases

- ID: D000007154

- Term: Immune System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC20

- Name: Immune System Diseases

### Condition Browse Module - Browse Leaves

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: HIGH

- As Found: Diabetes

- ID: M849

- Name: Latent Autoimmune Diabetes in Adults

- Relevance: HIGH

- As Found: Latent Autoimmune Diabetes in Adults

- ID: M7117

- Name: Diabetes Mellitus, Type 1

- Relevance: HIGH

- As Found: Autoimmune Diabetes

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25403

- Name: Glucose Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M4629

- Name: Autoimmune Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003920

- Term: Diabetes Mellitus

- ID: D000003922

- Term: Diabetes Mellitus, Type 1

- ID: D000071698

- Term: Latent Autoimmune Diabetes in Adults

### Intervention Browse Module - Ancestors

- ID: D000014815

- Term: Vitamins

- ID: D000018977

- Term: Micronutrients

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000050071

- Term: Bone Density Conservation Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: BDCA

- Name: Bone Density Conservation Agents

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: Vi

- Name: Vitamins

- Abbrev: AA

- Name: Amino Acids

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: LOW

- As Found: Unknown

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: LOW

- As Found: Unknown

- ID: M17550

- Name: Vitamin D

- Relevance: HIGH

- As Found: Ultrasound

- ID: M6003

- Name: Cholecalciferol

- Relevance: LOW

- As Found: Unknown

- ID: M17558

- Name: Vitamins

- Relevance: LOW

- As Found: Unknown

- ID: M257732

- Name: Aluminum sulfate

- Relevance: LOW

- As Found: Unknown

- ID: M21009

- Name: Micronutrients

- Relevance: LOW

- As Found: Unknown

- ID: M16885

- Name: Trace Elements

- Relevance: LOW

- As Found: Unknown

- ID: T442

- Name: Cholecalciferol

- Relevance: LOW

- As Found: Unknown

- ID: T479

- Name: Vitamin D3

- Relevance: LOW

- As Found: Unknown

- ID: T440

- Name: Calciferol

- Relevance: LOW

- As Found: Unknown

- ID: T5

- Name: Glutamic Acid

- Relevance: HIGH

- As Found: Implantable Cardioverter Defibrillator

### Intervention Browse Module - Meshes

- ID: D000014807

- Term: Vitamin D

### Misc Info Module

- Version Holder: 2024-05-24
