RECRUITING

Repeat BCG Vaccinations for the Treatment of New Onset Type 1 Diabetes in Children Age 8-<18 Years

Conditions

Diabetes Mellitus Type 1 Diabetes Diabetes Type1 Autoimmune Diabetes Type One Diabetes Mellitus Type I Autoimmune Diabetes Insulin Dependent Diabetes Mellitus 1 IDDM

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to investigate if repeat bacillus Calmette-Guérin (BCG) vaccinations can confer a beneficial immune and metabolic effect in new onset pediatric Type 1 diabetes.

Official Title

Repeat BCG Vaccinations for the Treatment of New Onset Type 1 Diabetes in Children Age 8-<18 Years

Quick Facts

Study Start:2023-05-04

Study Completion:2028-05

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05866536

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:8 Years to 17 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD

Inclusion Criteria	Exclusion Criteria
* Male or female, Age 8 - \<18 years at the time of study entry and \<18 at the time of randomization. * Type 1 diabetic subjects diagnosed more than 3 months ago and less than 12 months ago. * Previously diagnosed with type 1 diabetes mellitus (based on clinical judgement and supported by laboratory analysis as per local guidelines) prior to study enrollment by WHO/ADA diagnostic criteria for glucose levels (FPG = 7.0 mmol/L \[126 mg/dL\]) or plasma glucose levels 2-hours after 75-gm oral glucose load of = 11.1 mmol/L (200 mg/dL) or a casual plasma glucose \>200 mg/dL with symptoms. * Presence of one or more of the following: antibodies to glutamic acid decarboxylase (GAD), islet cell autoantibody (ICA), protein tyrosine phosphatase-like protein antibodies (IA-2), Insulin autoantibodies (IAA), zinc transporter 8 antibodies (ZnT8). * Ongoing daily treatment with insulin prior to the screening visit. * HIV antibody negative, M. tuberculosis (TB) negative (QuantiFERON-TB test negative), human chorionic gonadotropin (hCG) negative. * Normal CBC and chemistries and only Grade 1 creatinine elevations. * Informed consent and child assent, as age-appropriate, obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. Legally Acceptable Representative (LAR) of the Subject must sign and date the Informed Consent Form (according to local requirements). The child must sign and date the Child Assent Form or provide oral assent, if required according to local requirements. * Ability and willingness to adhere to the protocol, including performing self-measured plasma glucose profiles (Subject and LAR(s) should be evaluated as a unit).	* History of tuberculosis, positive interferon-gamma release assay (IGRA, also known as the QuantiFERON-TB test), including a test with a high reactivity to mycobacteria of non-tuberculosis variety. * History of prior BCG vaccination, positive T-spot tuberculosis test or a T-spot test showing significant Mycobacteria exposure. * Not born in the US or born in a country with mandatory BCG vaccinations. * Previous participation in the treatment group in biologic or drug intervention trials for Type 1 diabetes such as anti-CD3. * Simultaneous participation in any other clinical trial while enrolled in this clinical trial or participation in another clinical trial within 28 days before the screening visit Note: Clinical trials do not include non-interventional studies. * Current participation in the Phase I or II BCG clinical trial or other immunotherapy diabetes clinical trials. * Current treatment with aspirin \> 160 mg/day or chronic, daily NSAIDs. * Current treatment with chronic antibiotics that interfere with BCG viability. * Current treatment with glucocorticoids (other than intermittent nasal or eye steroids, asthma inhaler, or topical steroids), or disease or condition likely to require high dose steroid or immunosuppressive therapy. This does not include replacement therapies for conditions such as growth hormone deficiencies, Addison's disease, or hypothyroidism. * Anticipated initiation or change in concomitant medication in excess of 14 days known to affect glucose metabolism (e.g. thyroid hormones, corticosteroids). * Currently on or planning to be taking any oral type 2 diabetes drug or other oral blood sugar lowering medication. * Treatment with any medication for the indication of diabetes other than stated in the inclusion criteria in a period of 90 days before screening. * History of keloid formation * History of lupus * Monogenetic diabetes * Diabetes secondary to cystic fibrosis. * History of type 2 diabetes or severe obesity. * Known hypoglycemic unawareness or recurrent severe hypoglycemic episodes as judged by the Investigator. * More than one episode of diabetic ketoacidosis requiring hospitalization within the last 90 days prior to the screening. * History of recurrent ketoacidosis with hospitalizations due to non-compliance. * History of active proliferative diabetic retinopathy. * History or evidence of chronic kidney disease (serum creatinine \> 1.5mg/dL), significant protein in the urine, or other significant and/or active diabetes related complication. * History of significant neuropathy, myocardial infarcts, active psychiatric disease that might preclude travel and long-term participation, dementia, foot ulcers, severe diabetes non-compliance, amputations, or kidney disease. * Diagnosis of malignant neoplasms within the last five years prior to the screening visit. * History of medical condition(s) that may impact red blood cell turnover such as polycythemia, chronic anemia, vitamin E infusion, transfusion, sickle cell or thalassemia, vitamin C injections, lead poisoning, uremia, or asplenia. * Other chronic conditions, diseases and/or treatments associated with increased risk of serious side effects or morbidities. Such conditions that increase the risk of infections with immunosuppressive therapies for other autoimmune diseases, patients with a previous history of severe burns, or treatment with immunosuppressive medications of any type (e.g., imuran, methotrexate, cyclosporine, etanercept, infliximab) for any reason. * History of chronic infectious disease, such as HIV or untreated or active hepatitis. * Living with someone who is immunosuppressed and/or at high risk for infectious diseases (for example, HIV+ or taking immunosuppressive medications for any reason) as judged by the investigator. * Known or suspected hypersensitivity to trial products or related products. * Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice). * Any condition, which, in the opinion of the Investigator, might jeopardize the Subject's safety or compliance with the protocol. * Diabetes lacking at least 1 diabetes-specific autoantibody. * Age of diabetes onset \<1 * Current BMI of \<5th percentile or \>95th percentile * Blood pressure \>90th percentile for their age and sex * Temperature \>98.6 F * Heart rate outside of 50-120 bpm

Inclusion Criteria

Exclusion Criteria

* Male or female, Age 8 - \<18 years at the time of study entry and \<18 at the time of randomization.
* Type 1 diabetic subjects diagnosed more than 3 months ago and less than 12 months ago.
* Previously diagnosed with type 1 diabetes mellitus (based on clinical judgement and supported by laboratory analysis as per local guidelines) prior to study enrollment by WHO/ADA diagnostic criteria for glucose levels (FPG = 7.0 mmol/L \[126 mg/dL\]) or plasma glucose levels 2-hours after 75-gm oral glucose load of = 11.1 mmol/L (200 mg/dL) or a casual plasma glucose \>200 mg/dL with symptoms.
* Presence of one or more of the following: antibodies to glutamic acid decarboxylase (GAD), islet cell autoantibody (ICA), protein tyrosine phosphatase-like protein antibodies (IA-2), Insulin autoantibodies (IAA), zinc transporter 8 antibodies (ZnT8).
* Ongoing daily treatment with insulin prior to the screening visit.
* HIV antibody negative, M. tuberculosis (TB) negative (QuantiFERON-TB test negative), human chorionic gonadotropin (hCG) negative.
* Normal CBC and chemistries and only Grade 1 creatinine elevations.
* Informed consent and child assent, as age-appropriate, obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. Legally Acceptable Representative (LAR) of the Subject must sign and date the Informed Consent Form (according to local requirements). The child must sign and date the Child Assent Form or provide oral assent, if required according to local requirements.
* Ability and willingness to adhere to the protocol, including performing self-measured plasma glucose profiles (Subject and LAR(s) should be evaluated as a unit).

* History of tuberculosis, positive interferon-gamma release assay (IGRA, also known as the QuantiFERON-TB test), including a test with a high reactivity to mycobacteria of non-tuberculosis variety.
* History of prior BCG vaccination, positive T-spot tuberculosis test or a T-spot test showing significant Mycobacteria exposure.
* Not born in the US or born in a country with mandatory BCG vaccinations.
* Previous participation in the treatment group in biologic or drug intervention trials for Type 1 diabetes such as anti-CD3.
* Simultaneous participation in any other clinical trial while enrolled in this clinical trial or participation in another clinical trial within 28 days before the screening visit Note: Clinical trials do not include non-interventional studies.
* Current participation in the Phase I or II BCG clinical trial or other immunotherapy diabetes clinical trials.
* Current treatment with aspirin \> 160 mg/day or chronic, daily NSAIDs.
* Current treatment with chronic antibiotics that interfere with BCG viability.
* Current treatment with glucocorticoids (other than intermittent nasal or eye steroids, asthma inhaler, or topical steroids), or disease or condition likely to require high dose steroid or immunosuppressive therapy. This does not include replacement therapies for conditions such as growth hormone deficiencies, Addison's disease, or hypothyroidism.
* Anticipated initiation or change in concomitant medication in excess of 14 days known to affect glucose metabolism (e.g. thyroid hormones, corticosteroids).
* Currently on or planning to be taking any oral type 2 diabetes drug or other oral blood sugar lowering medication.
* Treatment with any medication for the indication of diabetes other than stated in the inclusion criteria in a period of 90 days before screening.
* History of keloid formation
* History of lupus
* Monogenetic diabetes
* Diabetes secondary to cystic fibrosis.
* History of type 2 diabetes or severe obesity.
* Known hypoglycemic unawareness or recurrent severe hypoglycemic episodes as judged by the Investigator.
* More than one episode of diabetic ketoacidosis requiring hospitalization within the last 90 days prior to the screening.
* History of recurrent ketoacidosis with hospitalizations due to non-compliance.
* History of active proliferative diabetic retinopathy.
* History or evidence of chronic kidney disease (serum creatinine \> 1.5mg/dL), significant protein in the urine, or other significant and/or active diabetes related complication.
* History of significant neuropathy, myocardial infarcts, active psychiatric disease that might preclude travel and long-term participation, dementia, foot ulcers, severe diabetes non-compliance, amputations, or kidney disease.
* Diagnosis of malignant neoplasms within the last five years prior to the screening visit.
* History of medical condition(s) that may impact red blood cell turnover such as polycythemia, chronic anemia, vitamin E infusion, transfusion, sickle cell or thalassemia, vitamin C injections, lead poisoning, uremia, or asplenia.
* Other chronic conditions, diseases and/or treatments associated with increased risk of serious side effects or morbidities. Such conditions that increase the risk of infections with immunosuppressive therapies for other autoimmune diseases, patients with a previous history of severe burns, or treatment with immunosuppressive medications of any type (e.g., imuran, methotrexate, cyclosporine, etanercept, infliximab) for any reason.
* History of chronic infectious disease, such as HIV or untreated or active hepatitis.
* Living with someone who is immunosuppressed and/or at high risk for infectious diseases (for example, HIV+ or taking immunosuppressive medications for any reason) as judged by the investigator.
* Known or suspected hypersensitivity to trial products or related products.
* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice).
* Any condition, which, in the opinion of the Investigator, might jeopardize the Subject's safety or compliance with the protocol.
* Diabetes lacking at least 1 diabetes-specific autoantibody.
* Age of diabetes onset \<1
* Current BMI of \<5th percentile or \>95th percentile
* Blood pressure \>90th percentile for their age and sex
* Temperature \>98.6 F
* Heart rate outside of 50-120 bpm

Contacts and Locations

Study Contact

Denise L Faustman, MD, PhD

CONTACT

617-726-4084

diabetestrial@partners.org

Principal Investigator

Denise L Faustman, MD, PhD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

Immunobiology Labs CNY 149

Charlestown, Massachusetts, 02129

United States

Collaborators and Investigators

Sponsor: Massachusetts General Hospital

Denise L Faustman, MD, PhD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-05-04

Study Completion Date2028-05

Study Record Updates

Study Start Date2023-05-04

Study Completion Date2028-05

Terms related to this study

Keywords Provided by Researchers

Diabetes Mellitus
Type One Diabetes Mellitus
Type I Autoimmune Diabetes Insulin Dependent Diabetes Mellitus 1 IDDM

Additional Relevant MeSH Terms

Diabetes Mellitus
Type 1 Diabetes
Diabetes Type1
Autoimmune Diabetes