Type 1 Diabetes - Ongoing clinical trials of immune suppressant therapy

What your doctor is reading or should be.
April 16, 2008

(photo courtesy of nicointhebus (Nicolas Monnot)

The recent onset of diabetes in the child of friends of ours led me to the registry of clinical trials. There are 68 studies in the registry recruiting children for studies on type 1 diabetes in children. Our friends, whose son is 8, had already contacted an investigator for one of the trials who encouraged their participation.

This trial and several others take advantage of new understandings of the proximate causes of Type 1 diabetes now believed to be related to autoimmunity, or said another way, due to the body somehow reacting against itself, or parts of itself, in this case the beta cells in the pancreas that make insulin. The result is a gradual decrease in beta cells and usually the gradual onset of diabetes, high blood sugars and later the vascular and other complications that may arise.

The idea behind many of the trials of aggressive intervention in new onset Type 1 diabetes is to try to slow the gradual destruction of beta cells by interfering with the autoimmune system that is producing antibodies that stimulate T-Lymphocytes that are causing the damage. One way to do this is to block the antibody receptor site on the T-Lymphocyte.

One of the trials (registry number NCT00129259) involves the molecule hOKT3gammal (Ala-Ala), which is administered intravenously over a 14 day period. This regimen is repeated a year later. The aim is to determine if patients receiving the molecular antibody (drug) will retain more of their ability to produce insulin. In a previous study of a very small number of patients, this seemed to be the case with about 70% of patients with new onset Type 1 diabetes receiving the drug maintaining or increasing their insulin production compared to about only 20% of control patients, who received usual care for their diabetes.<1> For information on this trial see www.clinicaltrials.gov


Interpretation

While this is an exciting area of new research, the results so far are but preliminary. All the trials do not rule out the possibility of the results being due to chance (as the number of patients in the trials is small) or bias (most studies are open label - meaning that the investigators and the patient’s physicians know whether their patient is in the treatment or control group).

Also, the immune system is complex, important for a very large number of body functions and protections and incompletely understood. Alterations in T-cells, a key component of our immune systems, may generate adverse events during the trials (so far no serious events have been detected) or later. Early trials involving small numbers of patients are unlikely to detect infrequent yet serious adverse events.

Implications

For the patient and family

Type 1 diabetes always comes as an unexpected and unpleasant surprise. The possibility of a treatment that could reverse or slow the onset of insulin-dependent diabetes, or reduce the need for insulin and perhaps even delay or deny the onset of known adult complications of diabetes, generates hope. It is unlikely, however,  that the drugs being studied will be released for clinical use for at least several years.

Participation in a trial may provide parents with a way to express their non-competing feelings of hope and anxiety by ‘doing something’. Unfortunately, outside the US there are few trials to available.

To find a trial in your area, use the search function at the registry (www.clinicltrials.gov) and enter the search terms: type 1 diabetes, open studies, interventional studies, child and country. The trials are described and contact information is provided (usually a telephone number and address).

For Society

While type 1 diabetes is not common, it is a serious illness and deserves our attention, research and treatment resources. Finding a way to prevent the illness or severely limit its effects would provide relief to many families, especially those who harbour the genetic signatures that in some way enable the disease to take hold.

Reference

Herold KC, Gitelman SE, Masharani U. et al. A single course of anti-CD3 monocoloanal antibody hOKT3 1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes 2005;54:1763-9