Diabetes Mellitus, Type OnePhase 2NCT02081326
Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes
A Phase 2 study testing Bacillus Calmette-Guérin and Saline injection in people with Diabetes Mellitus, Type One and Diabetes Mellitus, Type I, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This Phase II RCT using multi-dose Bacillus Calmette-Guérin (BCG) in adults with juvenile or childhood onset diabetes is based on prior clinical trials showing that even with advanced disease and little of no remaining pancreas activity, HbA1c can be lowered. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Diabetes Mellitus, Type One, Diabetes Mellitus, Type I, Autoimmune Diabetes
- What is being tested?
- Bacillus Calmette-Guérin and Saline injection
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2015to Jul 2031
- Phase
- Phase 2
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 diabetes treated continuously with insulin from time of diagnosis
- Age 18-65
- HIV antibody negative
- Normal CBC
- HCG negative (females)
- Anti-GAD Positive (except for subjects with c-peptide <10pmol/L)
- Fasting or stimulated c-peptide between 5-200 pmol/L
- Participation in protocol #2001P001379, "Autoimmunity: In Vitro Pathogenesis and Early Detection"
Who cannot join
- History of chronic infectious disease such as HIV or hepatitis
- History of tuberculosis, TB risk factors, positive interferon-gamma release assay (IGRA, also known as the T-SPOT.TB test), or BCG vaccination
- Current treatment with glucocorticoids (other than intermittent nasal or eye steroids), or disease or condition likely to require steroid therapy
- Other conditions or treatments associated with increased risk of infections such as 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
- Current treatment with aspirin > 160 mg/day or chronic, daily NSAIDs
- Current treatment with antibiotics
Show all 13Show fewer
- History of keloid formation
- Average HbA1c over the past 5 years (or since diagnosis if duration is less than 5 years) <6.5 or > 8.5%
- History or evidence of chronic kidney disease (serum creatinine > 1.5mg/dL)
- History of proliferative diabetic retinopathy that has not been treated with laser therapy
- History of neuropathy, foot ulcers, amputations, or kidney disease
- Pregnant or not using acceptable birth control
- Living with someone who is immunosuppressed and/or at high risk for infectious diseases (for example HIV+ or taking immunosuppressive medications for any reason)
Trial locations and contacts
1 site in 1 country.
United States1 site
Immunobiology Labs CNY 149
Charlestown, Massachusetts, 02129
About this study
This Phase II RCT using multi-dose Bacillus Calmette-Guérin (BCG) in adults with juvenile or childhood onset diabetes is based on prior clinical trials showing that even with advanced disease and little of no remaining pancreas activity, HbA1c can be lowered. Prior clinical trials with this highly desired outcome include Phase 1B and two open label clinical trials (2007p001347; IND 10435). The mechanism of restored glucose control was independent of the pancreas; BCG restored regulated sugar transport (aerobic glycolysis) throughout the lymphoid system for normoglycemia.
In the planning for this 10 year long Phase II clinical trial, with first 5 year unblinding, Dr David Schoenfeld, Chief of Biostatics at MGH in SAP 0.0 modeled that 51 long term adult diabetic subjects randomized 2:1 with BCG vaccines over 5 years, would have high probably of repeating the past success in achieving lowered HbA1c in the Phase 1B clinical trial (2012P002243). This Primary outcome and the Primary study population in adults but with juvenile onset disease was the original and continuous outcome for this Phase II clinical trial (IND16434).
In addition to routine protocol changes throughout this study, additional studies were added. These same subjects were both studied in a concurrent Phase II and Phase III infectious disease adaptive clinical trial confirming that BCG provided protection from all infectious diseases and COVID-19 in this vulnerable population, confirming past work of many investigators in Europe (2020P001462). As an early added Exploratory outcome, the trial enrollment numbers were expanded to include latent autoimmune diabetes subjects (LADA), an autoimmune type of diabetes with adult onset. As was reported prior to this trial start, LADA adults lack the necessary lymphoid aerobic defects restored by BCG in the lymphocytes of juvenile onset subjects but have the very slow decay of the pancreas. The slow decay of the pancreas tested the Exploratory outcome of the ability of BCG to induce of T regulatory cells (Treg cells) to possibly halt continued loss of insulin in the pancreas i.e. the autoimmune disease attack of the insulin secreting insulin secreting islets and impact of C-peptide secondary outcomes. Throughout all protocols the study of proteomics was contemplated from collected samples at the end of the study. Proteomics revealed important protein changes related to Alzheimer's complications. The protocol was modified to also generate confirmatory data using FDA approved Alzheimer's diagnostics (IND16434; IND 181620). Additional changes to IND 16434 at the suggestion of the FDA included adding an additional study of PET FDG uptake scan to look for the organ systems wherein BCG induced improved sugar uptake. IND 16434 also allowed a limited number of subjects to have Expanded access. IND 16434 at the 5-year mark will be unblinded for the first data analysis of the 10-year study; placebo subjects can continue with or without the BCG and previous treated BCG can continue as placebo subjects during this "cross over study".
- Being tested
- Bacillus Calmette-Guérin, Saline injection
- Keywords
- Diabetes Mellitus, Type One, Diabetes Mellitus, Type I, Autoimmune Diabetes, Insulin Dependent Diabetes Mellitus 1, IDDM, COVID-19
- Medical subject headings
- Diabetes Mellitus, Diabetes Mellitus, Type 1, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bacillus Calmette-GuérinBiological
2 BCG vaccinations spaced 4 weeks apart during the first year and then 1 vaccination every year for the next 4 years
Saline injectionBiological
2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years
| Study group | Role | What they receive |
|---|---|---|
| Bacillus Calmette-Guérin | Experimental | 2 BCG vaccinations spaced 4 weeks apart during the first year and then 1 vaccination every year for the next 4 years Receives: Biological: Bacillus Calmette-Guérin |
| Saline injection | Placebo comparator | 2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years Receives: Biological: Saline injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in HbA1c values in juvenile onset type 1 diabetics
A change in the hemoglobin A1c (HbA1c) measurement compared to self
Measured: 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Secondary outcomes (3)
Insulin use in juvenile onset type 1 diabetics (AOO<21 years)
A change in insulin (IDAA1c) use as reported at study visits compared to self in juvenile onset type 1 diabetes.
Measured: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Endogenous insulin levels in the blood in juvenile onset type 1 diabetics (AOO<21 years)
A change in c-peptide and proinsulin levels (as an analog for endogenous insulin) in the blood compared to self.
Measured: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Autoimmunity in juvenile onset type 1 diabetes (AOO<21 years)
A change in autoantibodies and autoreactive T cells to monitor the drug mechanism for autoimmune changes.
Measured: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2014 (estimated)
- Study startJun 2015
- Primary completionJul 2029 (estimated)
- Study completionJul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type OneStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Denise Louise Faustman, MD, Massachusetts General Hospital
- Investigators
- Denise L Faustman, MD, PhD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02081326
- Sponsor's protocol ID
- 2013P002633
- Status last verified
- Apr 2026
- First submitted
- 4 Mar 2014
- Last updated
- 13 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Faustman DL, Lee A, Hostetter ER, Aristarkhova A, Ng NC, Shpilsky GF, Tran L, Wolfe G, Takahashi H, Dias HF, Braley J, Zheng H, Schoenfeld DA, Kuhtreiber WM. Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes. Cell Rep Med. 2022 Sep 20;3(9):100728. doi: 10.1016/j.xcrm.2022.100728. Epub 2022 Aug 15.
PubMed 36027906
Study at a glance
From the registry record, last updated by the sponsor on 13 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Repeat BCG Vaccinations for the Treatment of Established Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT02081326
- Acronym / sponsor ID
- 2013P002633
- Keywords
- Diabetes Mellitus, Type One, Diabetes Mellitus, Type I, Autoimmune Diabetes, Insulin Dependent Diabetes Mellitus 1, IDDM, COVID-19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Jun 2015
- Primary completion
- Jul 2029 (estimated)
- Study completion
- Jul 2031 (estimated)
- First posted
- 7 Mar 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This Phase II RCT using multi-dose Bacillus Calmette-Guérin (BCG) in adults with juvenile or childhood onset diabetes is based on prior clinical trials showing that even with advanced disease and little of no remaining pancreas activity, HbA1c can be lowered. Prior clinical trials with this highly desired outcome include Phase 1B and two open label clinical trials (2007p001347; IND 10435). The mechanism of restored glucose control was independent of the pancreas; BCG restored regulated sugar transport (aerobic glycolysis) throughout the lymphoid system for normoglycemia.
In the planning for this 10 year long Phase II clinical trial, with first 5 year unblinding, Dr David Schoenfeld, Chief of Biostatics at MGH in SAP 0.0 modeled that 51 long term adult diabetic subjects randomized 2:1 with BCG vaccines over 5 years, would have high probably of repeating the past success in achieving lowered HbA1c in the Phase 1B clinical trial (2012P002243). This Primary outcome and the Primary study population in adults but with juvenile onset disease was the original and continuous outcome for this Phase II clinical trial (IND16434).
In addition to routine protocol changes throughout this study, additional studies were added. These same subjects were both studied in a concurrent Phase II and Phase III infectious disease adaptive clinical trial confirming that BCG provided protection from all infectious diseases and COVID-19 in this vulnerable population, confirming past work of many investigators in Europe (2020P001462). As an early added Exploratory outcome, the trial enrollment numbers were expanded to include latent autoimmune diabetes subjects (LADA), an autoimmune type of diabetes with adult onset. As was reported prior to this trial start, LADA adults lack the necessary lymphoid aerobic defects restored by BCG in the lymphocytes of juvenile onset subjects but have the very slow decay of the pancreas. The slow decay of the pancreas tested the Exploratory outcome of the ability of BCG to induce of T regulatory cells (Treg cells) to possibly halt continued loss of insulin in the pancreas i.e. the autoimmune disease attack of the insulin secreting insulin secreting islets and impact of C-peptide secondary outcomes. Throughout all protocols the study of proteomics was contemplated from collected samples at the end of the study. Proteomics revealed important protein changes related to Alzheimer's complications. The protocol was modified to also generate confirmatory data using FDA approved Alzheimer's diagnostics (IND16434; IND 181620). Additional changes to IND 16434 at the suggestion of the FDA included adding an additional study of PET FDG uptake scan to look for the organ systems wherein BCG induced improved sugar uptake. IND 16434 also allowed a limited number of subjects to have Expanded access. IND 16434 at the 5-year mark will be unblinded for the first data analysis of the 10-year study; placebo subjects can continue with or without the BCG and previous treated BCG can continue as placebo subjects during this "cross over study".
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bacillus Calmette-Guérin | Experimental | Biological: Bacillus Calmette-Guérin2 BCG vaccinations spaced 4 weeks apart during the first year and then 1 vaccination every year for the next 4 years |
| Saline injection | Placebo comparator | Biological: Saline injection2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Type 1 diabetes treated continuously with insulin from time of diagnosis
- Age 18-65
- HIV antibody negative
- Normal CBC
- HCG negative (females)
Key exclusion criteria (13 listed)
- History of chronic infectious disease such as HIV or hepatitis
- History of tuberculosis, TB risk factors, positive interferon-gamma release assay (IGRA, also known as the T-SPOT.TB test), or BCG vaccination
- Current treatment with glucocorticoids (other than intermittent nasal or eye steroids), or disease or condition likely to require steroid therapy
- Other conditions or treatments associated with increased risk of infections such as 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
- Current treatment with aspirin > 160 mg/day or chronic, daily NSAIDs
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bacillus Calmette-Guérin2 BCG vaccinations spaced 4 weeks apart during the first year and then 1 vaccination every year for the next 4 years | Biological | Bacillus Calmette-Guérin |
| Saline injection2 injections spaced 4 weeks apart during the first year, then 1 injection per year for the next 4 years | Biological | Saline injection |
Primary outcome
Change in HbA1c values in juvenile onset type 1 diabetics
Time frame: 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
A change in the hemoglobin A1c (HbA1c) measurement compared to self
3 secondary outcomes
Insulin use in juvenile onset type 1 diabetics (AOO<21 years)
Time frame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Endogenous insulin levels in the blood in juvenile onset type 1 diabetics (AOO<21 years)
Time frame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Autoimmunity in juvenile onset type 1 diabetes (AOO<21 years)
Time frame: 4 weeks and 1, 2, 3, 4, and 5 years after initial BCG/placebo injection
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Apr 2026.
- Derived from this study: PubMed 36027906Faustman DL, Lee A, Hostetter ER, Aristarkhova A, Ng NC, Shpilsky GF, Tran L, Wolfe G, Takahashi H, Dias HF, Braley J, Zheng H, Schoenfeld DA, Kuhtreiber WM. Multiple BCG vaccinations for the prevention of COVID-19 and other infectious diseases in type 1 diabetes. Cell Rep Med. 2022 Sep 20;3(9):100728. doi: 10.1016/j.xcrm.2022.100728. Epub 2022 Aug 15.
- Faustman Lab Research WebsiteLink provided by the sponsor.
Related trials for Diabetes Mellitus, Type One
Not yet recruitingPhase 3
A Study to Evaluate the Effectiveness and Safety of the Drug AZD6234 for Managing Weight in Adults Who Are Obese or Overweight. These Participants May or May Not Also Have Type 2 Diabetes
Obesity, Overweight
RecruitingPhase 3
A Study to Evaluate Effect of AZD6234 in Adult Participants With Obesity or Overweight With Weight-related Comorbidity Without Type 2 Diabetes Mellitus
Obesity or Overweight
Not yet recruitingPhase 3
Oral VK2735 for Weight Management Phase 3 (SUNRISE 1)
Weight Loss
Enrolling by invitationObservational study
Universal Type 1 Diabetes Screening in Pediatrics
Type 1 Diabetes (T1D)
RecruitingPhase 3
A Research Study to Look at How Two Different Doses of CagriSema and One Dose of Semaglutide Help People Living With Obesity With or Without Type 2 Diabetes Lose Weight
Obesity, Type 2 Diabetes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Denise L Faustman, MD, PhD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Bacillus Calmette-Guérin and Saline injection in people with Diabetes Mellitus, Type One and Diabetes Mellitus, Type I, run by Massachusetts General Hospital at 1 site in United States.
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 8 inclusion and 13 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: under way, not looking for participants, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in HbA1c values in juvenile onset type 1 diabetics (time frame: 1, 2, 3, 4, and 5 years after initial BCG/placebo injection). 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 NCT02081326, which also lists 1 linked publication.
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 13 Apr 2026.