4 Promising New and Upcoming Clinical Trials for Type 1 Diabetes- September 2017

 

Type 1 Diabetes is a disease where your own immune system mistakenly attack the “pancreatic islets”- small clusters of cells in the pancreas that contain insulin-producing “beta” cells.

There is currently no cure for Type 1 Diabetes, although it can be managed. Type 1 diabetics must carefully time when and what they eat, monitor their blood glucose by pricking their fingers, and routinely inject themselves with insulin. This life-long struggle can be very annoying for patients. Furthermore, even with careful management, long-term complications generally develop over time. These complications include kidney failure, damage to the retina, heart disease, and foot ulcers. This highlights the need to find better ways to manage the disease.

In this article, we have summarised 4 clinical trials for Type 1 Diabetes. We explain the scientific reasoning behind each treatment and what the current findings are (including any potential side effects).

NOTE:

We did not receive any money from any of the following companies to write this article, nor did they ask us to publicise them. The trials are here because they stemmed from solid scientific research.

Before taking any actions, please consult your healthcare provider to determine whether or not you might benefit from these treatments.

 

1) The “T-Rex” study (T-regulatory cell therapy), Caladrius Biosciences, USA

What is the scientific basis of the study?

The name of the clinical trial is a pun on T-regs, short for “T-Regulatory cells”, which are a type of white blood cells involved in your immune system. T-regs distinguish which cells are harmful to your body, and which cells are not. So, they are crucial in preventing your immune system from mistakenly destroying your own healthy cells. As mentioned earlier, this is exactly the problem in Type 1 Diabetes: your immune system mistakenly destroys insulin-producing beta cells in your pancreas.

Indeed, Type 1 diabetics tend to have fewer T-reg cells in their blood. By increasing the number of T-reg cells, further destruction of the beta cells may be prevented. Studies in diabetic mice have shown that increasing the number of T-reg cells can slow the progression of diabetes, and in some cases, even reverse the disease. At the time of diagnosis, a Type 1 diabetes patient could still have around 20% of their beta cells in their pancreas. If protected from further damage, the remaining beta cells might be salvageable, decreasing the dependence on insulin (or, hopefully, removing this dependence completely).

Brief description of the clinical trial:

The aim of this Phase 2 trial is to see if this cell therapy (named “CLBS03” by Caladrius) is safe and effective in preserving the insulin-producing beta cells of children with Type 1 Diabetics.

Participants are randomly chosen to receive either the cell therapy or a placebo. Blood samples will be taken from the participants. T-reg cells will then be purified from the blood samples, and then multiplied in the lab (which takes around 2 weeks). The purified T-reg cells will then be returned to the same patient in a single dose.

The participants will be monitored over a period of 2 years (4 visits in the first month after the reintroduction of T-reg cells + 6 more follow-up visits over the following 23 months).

What are the findings so far?

56 out of the 111 aimed participants of this Phase 2 study have been treated. So far the findings have not been published yet (data on early progress of the treatment are due to be published later this year or early in 2018).

Prior to this study, a Phase 1 study on T-regs cell therapy in children had been completed. This study involved 22 children between the ages of 5-18 who were newly diagnosed with Type 1 Diabetes. 12 of the participants received the therapy, while the other 10 were non-treated controls. They were monitored for a period of 1 year following the treatment. No severe side effects were observed (one patient reported mild influenza and another reported mild gastroenteritis, but both were resolved within a few days), and the treatment resulted in increased insulin independence in participants receiving the cell therapy. Two children remained completely insulin independent at one year following the treatment.

Who is this study aimed at?

Children and adolescents (ages 8 – 17 years) recently diagnosed (< 100 days) with Type 1 diabetes.

Where is the study located?

USA:

  • California: Los Angeles, San Diego, San Francisco
  • Colorado: Aurora
  • Connecticut: New Haven
  • Florida: Gainesville, Miami
  • Indiana: Indianapolis
  • Massachusetts: Boston
  • Minnesota: Minneapolis
  • Missouri: Kansas City
  • North Dakota: Fargo
  • Oregon: Portland
  • South Dakota: Sioux Falls
  • Tennessee: Nashville
  • Texas: Houston

Who is running the trial & how to get in touch?

Caladrius Biosciences and Sanford Health

Contact details at individual trial sites are listed here.

ClinicalTrials.gov identifier: NCT02691247

Is there a similar treatment already available?

There are currently no similar treatments approved by the FDA for Type 1 Diabetes, although there are a few other clinical trials that are based on a very similar concept- e.g this one.

 

 

2) GNbAC1 antibody, GeNeuro, Australia

What is the scientific basis of the study?

GNbAC1 targets a protein called “Envelope (ENV) protein”. ENV is a protein that are present in the pancreas of Type 1 diabetics. There are evidence to suggest that this presence of ENV plays a crucial role in the development Type 1 Diabetes. For example, when the ENV protein is introduced to the pancreas of mice, it leads to hyperglycaemia (excess blood sugar) and insulitis (infiltration of white blood cells to the pancreas, leading to the destruction of insulin-producing cells) in the animals, similar to Type 1 Diabetes in humans.

Previous studies have also shown that GNbAC1 can block this ENV protein. Diabetic mice treated with GNbAC1 could maintain insulin production. So, GNbAC1 shows promise for treating Type 1 Diabetics.

ENV does not have any known function in the body, which means that targeting this protein with GNbAC1 is expected to be safe in humans.

Brief description of the clinical trial:

This is a randomized, placebo-controlled study (i.e. patients will receive either GNbAc1 or a placebo) in 60 recently diagnosed Type 1 Diabetics across Australia.

The aim of this Phase 2a study is to test GNbAC1’s safety, and its benefits in the functions of the pancreas and insulin production in Type 1 Diabetics. The participants will receive 6 consecutive 4-weekly injections of GNbAC1, and then monitored for 20 weeks.

The last patient enrolment is expected by the end of 2017 and preliminary results are expected in late 2018.

What are the findings so far?

The first patient on the trial received the treatment on 19 June 2017. So far no updates has been posted.

GNbAC1 is also currently being tested for treating Multiple Sclerosis. So far, 260 patients have been treated with either GNbAc1 or a placebo. Four studies published in 2016 suggest that GNbAC1 at various doses is well tolerated amongst the participants, with very few side effects reported during the duration of the study, as well as at a 12-month follow up. The side effects reported included flu-like symptoms and mild chest pains. (The studies are here, here, here, and here).

Who is this study aimed at?

Adults (18-45 years) diagnosed with Type 1 diabetes in the past 4 years.

Where is the study located?

Various locations in Australia- Currently recruiting in NSW, VIC, QLD, with SA in the future.

Who is running the trial & how to get in touch?

Eastern Clinical Research Unit of Monash University and Southern Star Research Pty Ltd.

Contacts:

Sam Oates, Ph: +61 2 9011 6266, Email: soates@southernstarresearch.com

ClinicalTrials.gov identifier: NCT03179423

Is there a similar treatment already available?

No- targeting ENV protein for diabetes is a novel concept.

 

 

3) Stem-cell implant to replace insulin-producing cells, ViaCyte, Canada

What is the scientific basis of their study?

“Stem cells” are precursors for many different types of cells in your body. They are kind of like blank tiles in Scrabble- you could use them to make any other letters (or in this case, cells). Given the right conditions, stem cells can develop into other cell types, such as heart cells, lung cells, and the beta cells in your pancreas that produce insulin.

A new product called “VC-02” (also known as “PEC-Direct”) is a credit card-sized pouch that contains embryonic stem cells. It would be implanted just under the skin of the patient, usually in the lower back. Several weeks after implantation, the stem cells are expected to “mature” into islet cells (which include beta cells). These cells would produce insulin to control blood glucose levels – just as a normal pancreas would. If successful, VC-02 hopes to eliminate the need for insulin injections and glucose monitoring.

In a way, this treatment would mimic pancreas transplants from organ donors. This organ transplant method has been used successfully for Type 1 Diabetes for decades, but was always limited by a shortage of donor organs. The stem cells in VC-02, on the other hand, can be multiplied easily in the lab, thereby overcoming the limitations faced by traditional pancreas transplant.

Brief description of the clinical trial:

The primary goal of this Phase 1 trial is to assess the safety of VC-02 over a period of 4 months after the implantation of the product. The participants will also be monitored for their insulin production, dependence on insulin injections, and incidence of hypoglycemic events (low blood sugar) over this period.

While VC-02 could potentially make Type 1 Diabetes a lot more manageable, it is not really a “true” cure for this autoimmune disease. VC-02 would merely replace the damaged cells; it does not actually address the cause of the damage (i.e. an overactive immune system). While the pouch provide the cells some protection from being rejected and destroyed by the patient’s immune system, the patients will still need to take immunosuppressant drugs– this is the same case for patients receiving organ transplant to prevent the new cells from being rejected.

What are the findings so far?

This study with VC-02 is very new. So far only 2 people have received the implant, and no data has been published. Any adverse side-effects are not yet known, but the potential risks listed by the University of Alberta include surgical risks (e.g. pain, bleeding, bruising, tenderness, redness) where the incisions are made for the implant, hypoglycemia (low blood sugar) events, and immune or inflammatory reactions.

A similar device made by the same company, VC-01, has already been safely tested in 19 people with diabetes. This study used a smaller numbers of stem cells in the implant.

Who is this study aimed at?

Adults (18-65 years old) who have had Type 1 diabetes for 5+ years.

The participants must also have a stable diabetic treatment, and have never had previous islet cell, kidney, or pancreas transplant.

Where is the study located?

Canada: Edmonton (University of Alberta Hospital)

The company also expects to expand the trial to additional centers in the USA (UC San Diego- Altman Clinical Trials Research Institute and the University of Minnesota) in the coming months.

Who is running the trial & how to get in touch?

ViaCyte and University of Alberta Hospital

Ph: (+1) 780-407-1501

Email: parastoo@islet.ca

ClinicalTrials.gov identifier: NCT03162926

Is there a similar treatment already available?

No. However, the goal of the stem cell implant is to mimic the pancreas in producing insulin. So as mentioned earlier, in a way this treatment is similar to a pancreas or islet cell transplant, which are already offered in the clinic for decades.

There are a few other clinical trials using stem cells for diabetes (e.g. this one and this one), but they have not received approval yet by the FDA.

Although there are many “stem cell clinics” offering stem cell therapies throughout the USA, South America, Russia, China, and India, please note that stem cell treatment for diabetes has not been approved by the FDA or any other international regulatory bodies, so there is absolutely no guarantee that they’re effective nor safe. Read more about the dangers of “stem cell tourism” here.

 

 

4) REMD-477- a drug that blocks glucagon, REMD Biotherapeutics, Inc., USA

What is the scientific basis of the study?

Glucagon is a hormone released by the pancreas when the concentration of glucose in the blood is too low. When glucagon is released, it causes the liver to make glucose, which is then released into the bloodstream to correct the glucose level back to normal. It is essentially the opposite of insulin (which is released when the blood glucose levels is high); glucagon and insulin levels needs to be balanced to keep an optimal blood glucose level.

Diabetics not only have a decrease in insulin, but they also have an increase in glucagon too, which throws this balance completely out of whack and results in really high levels of blood glucose. So, a drug that can block glucagon could also help reduce blood glucose levels. Indeed, previous studies in diabetic mice have shown that blocking glucagon can normalize blood glucose levels without the need for insulin injection, and does not result in hypoglycemia (low glucose levels).

This is exactly the theory behind REMD-477, which binds to the “receptor” for glucagon (therefore blocking glucagon and rendering it more or less useless). By blocking glucagon, REMD-477 decreases the amount of sugar produced by the liver, which could mean that diabetics will not need insulin injections as often.

Brief description of the clinical trial:

A new Phase 2 clinical trial has been set to test whether multiple doses of this REMD-477 is safe, and whether it can decrease insulin requirements. This trial has been registered, but is not yet open for participant recruitment.

What are the findings so far?

The Phase 1 clinical trial of REMD-477 was very recently completed. This initial phase tested a single dose of the drug on 21 participants. The results of this study was presented at the American Diabetes Association’s 77th Scientific Sessions in San Diego on 13 June 2017.

In the study, 10 patients were given a single injection of 70mg of REMD-477, while the other 11 were given a placebo. The glucose levels and the daily insulin requirements of the participants were monitored. The participants were given identical meals to try ensure that the results are independent of what they eat.

Two days after the injection was given, the patients treated with REMD-477 reduced the amount of daily insulin use by 32% compared to those who received a placebo. They also spent significantly more time in the target glucose range compared to the placebo recipients, and did not have an increased risk of hypoglycemia. The average blood glucose concentration also remained lower in patients treated with REMD-477 even three weeks after the injection was given.

In terms of the safety of the drug, the study reported that REMD-477 was well tolerated amongst the participants.

Who is this study aimed at?

Type 1 diabetics 18-65 years old, who have used insulin for at least 8 weeks.

Where is the study located?

No contacts is provided for this Phase 2 trial yet, but the Phase 1 study was run in San Diego (California), and St. Louis (Missouri), USA.

Who is running the trial & how to get in touch?

REMD Biotherapeutics.

This Phase 2 study is still not recruiting yet. Keep an eye out on the ClinicalTrials.gov page here for any contact information added in the future.

ClinicalTrials.gov identifier: NCT0311799

Is there a similar treatment already available?

There are currently no other treatments that block glucagon approved for Type 1 diabetes. There are treatments for Type 2 diabetes that can decrease glucagon production (e.g. incretin mimetics and DPP-4 inhibitors); they’re mechanistically different to REMD-477.

 

About Rina Soetanto

Rina Soetanto is currently doing her PhD in molecular biology. She also has an extensive background in pharmacology and pre-clinical cancer research, as well as an undergraduate science degree from the Australian National University with a double major in neuroscience and immunology.

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