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Recap claims ‘clinical validity’ from phase 1 diabetes trial. Isn’t that what phase 2 and 3 trials are for?

BCG vaccine leads to long-term blood sugar improvement in type 1 diabetes patients

Our Review Summary

insulin injectionThis release summarizes a phase I clinical trial that looks at the effect of bacillus Calmette-Guérin (BCG) vaccine on hemoglobin levels (HbA1c) in 52 adults with type I diabetes and 230 people who received no treatment but contributed blood samples.

HbA1c is a measure of average blood sugar levels over the preceding three months.

The study documented moderate reductions in HbA1c during the last 5 years of this 8-year study. The release would have been improved had it included absolute rather than relative numbers and a clarification of whether study participants were on insulin at the time of the study. Other factors could have contributed to the reduction of HbA1c levels over an 8-year period.

The STAT story on this same research, which we also reviewed, focused on a smaller group of 9 patients who’ve been followed for more than 5 years.

 

Why This Matters

Type I diabetes accounts for about 5-10% of all diabetes and can occur in both adults and children. It’s believed to be caused primarily by the auto-immune destruction of the insulin-producing (beta) cells of the pancreas, making people who have it dependent on injected insulin.There is currently no cure for type 1 diabetes aside from pancreatic transplant.

It’s important to bear in mind that HbA1c levels are commonly used as a  surrogate marker in diabetes research. Reductions in this marker don’t necessarily equate with less complications or better outcomes in people with either type I or type 2 diabetes and studies using HbA1c as an intermediate outcome have been limited by their short follow-up and linkage to long-term, clinically meaningful, outcomes.

Criteria

Does the news release adequately discuss the costs of the intervention?

Not Satisfactory

The cost of the bacillus Calmette-Guérin (BCG) vaccine is not mentioned.

Although the wholesale price is usually less than $1 US dollar, the cost in the United States usually runs between $100 to $200.

Does the news release adequately quantify the benefits of the treatment/test/product/procedure?

Not Satisfactory

The news release mentions only relative, not absolute numbers when describing the results in just 52 type 1 patients:

  • HbA1c dropped more than 10% at 3 years after treatment with BCG vaccine (2 doses, 4 weeks apart).
  • Levels dropped 18% at 4 years.

It’s stated that an average HbA1c level of 6.65 was achieved (normal is below 6.0, with many doctors shooting for below 6.5 in people with type 1 diabetes) and the reduction was maintained over the last 5 years of the 8-year-long trial.

Does the news release adequately explain/quantify the harms of the intervention?

Not Satisfactory

No harms of the vaccine are mentioned.

It’s been given to humans since the 1920s and side effects, including allergic reaction to this live vaccine, have been well documented. It should be avoided in anyone with decreased immune function.

Of note, a  point is made that in those study subjects who received the vaccine, there were “no reports of severe hypoglycemia.”

Does the news release seem to grasp the quality of the evidence?

Satisfactory

This trial was an extension of a short-term (20 week trial) published in 2012 that showed only a modest, temporary increase in insulin production. This much longer term trial analyzed data from 282 study volunteers (52 with type 1 diabetes) and 230 who contributed blood samples.

The adults with type 1 were treated with BCG and had their HbA1c levels followed for 8 years, presumably while still on insulin (although the news release does not make this clear).

We’re given the percent change in their HbA1c levels between years 3 and 8 — a reduction of nearly 20% —  a moderate improvement over a long-term.

A second arm of this study was a laboratory analysis looking for what might account for the effect of BCG on blood sugar. The authors speculate that their data suggest a metabolic shift in glucose metabolism from oxidative (the most common pathway by which cells convert glucose into energy) to an aerobic metabolism characterized by greater glucose utilization by cells called aerobic glycolysis.

Does the news release commit disease-mongering?

Satisfactory

None. Type I diabetes is common and can be difficult to treat.

Does the news release identify funding sources & disclose conflicts of interest?

Satisfactory

According to the news release the study “is entirely funded by private philanthropy from individuals and family foundations.”

No conflicts of interest are reported in the published study.

Does the news release compare the new approach with existing alternatives?

Not Applicable

There are no known alternatives to insulin so we’ll rate this Not Applicable. People with type I diabetes are dependent on insulin to manage their disease because their bodies to not produce insulin. It is the only established treatment other than pancreas transplant with other interventions — like diet and exercise — being secondary to the insulin replacement.

To date, their are no established forms of therapy based solely on an autoimmune mechanism to lower blood sugars as BCG is claimed to do by the study authors.

Does the news release establish the availability of the treatment/test/product/procedure?

Satisfactory

It’s mentioned that BCG has been used for “almost a century” to prevent tuberculosis.

(Of note, it’s also been used for non-invasive bladder cancer.)

Does the news release establish the true novelty of the approach?

Not Satisfactory

The release suggests that the study is “clinical validation” of the vaccine’s ability to lower blood sugars to “near normal levels.” But can a small phase 1 trial be used to claim validity? Phase 2 and 3 trials are also needed.

The news release also notes that the lead author published a 20-week, phase I trial in 2012 which showed only temporary HbA1c reduction.

Does the news release include unjustifiable, sensational language, including in the quotes of researchers?

Satisfactory

There is no blatant sensationalism.

However, claiming “clinical validation of the potential” of the vaccine to do something seems like weasel words, particularly in the context of a phase 1 trial.

Total Score: 5 of 9 Satisfactory

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