NCT01762657: IIT

A Phase 3, Randomized, Double-Blind, Multinational, Placebo-Controlled Study to Evaluate the Safety and Efficacy in Diminishing Insulin Requirements Utilizing Oral Cyclosporine With Oral Lansoprazole in Children and Adults With Existing Type 1 Diabetes Mellitus

Withdrawn Phase 3 Last updated 17 April 2016

What this trial tests

Phase 3 trial testing Oral Cyclosporine and Oral Lansoprazole in Type 1 Diabetes. Withdrawn.

Timeline

1 September 2014

Primary endpoint
1 September 2015

1 September 2015

Quick facts

Lead sponsor	Perle Bioscience, Inc.
Phase	Phase 3
Status	Withdrawn
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Start date	1 September 2014
Primary completion	1 September 2015
Estimated completion	1 September 2015

Drugs / interventions tested

• Oral Cyclosporine and Oral Lansoprazole — full drug profile →
• Placebos — full drug profile →

Conditions studied

• Type 1 Diabetes — all drugs for Type 1 Diabetes →

Sponsor

Perle Bioscience, Inc. — full company profile →

Who can join

Adults 8 to 60, any sex, with Type 1 Diabetes. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Insulin Requirements Among Patients Treated with Oral Cyclosporine and Oral Lansoprazole
  Time frame: 26 and 52 weeks

Sponsor's own description

The purpose of this study is to determine if oral Cyclosporine A and oral Lansoprazole are effective in rendering patients with existing type 1 diabetes, insulin independent. This two-arm study was designed to evaluate the safety and efficacy for insulin independence by utilizing the FDA-approved oral immune tolerance agent, Cyclosporine A, and the FDA-approved proton-pump inhibitor, Lansoprazole. Lansoprazole and other proton-pump inhibitors increase gastrin levels. Gastrin was initially shown to have the potential to increase new beta cell formation in 1955 (Zollinger RM and Ellison EH. Ann Surg. 1955;142(4):709-23).

Studies with the immune tolerance agent, Cyclosporine A, previously demonstrated that among recently diagnosed type 1 diabetes patients, insulin independence was achieved in as many as 67.5% of patients within 7 weeks of therapy (Bougneres PF et al. N Engl J Med. 1988:17;318(11):663-70). Cyclosporine A protected the remaining beta cells from further autoimmune attack, but over time, there was limited beta cell regeneration, and insulin was ultimately required by all patients. Therefore, this study proposes the usage of Cyclosporine A with a beta regeneration agent.

Follow-up studies for up to 13 years among 285 type 1 patients utilizing Cyclosporine A for 20 months, did not demonstrate renal or other side effects (Assan R. et al. Diabetes Metab Res Rev. 2002;18(6):464-72). Human clinical trials with gastrin and epidermal growth factor demonstrated reductions in daily insulin requirements by much as 75% within 3 months following four weeks of therapy among existing type 1 diabetes patients (Transition Therapeutics, March 5, 2007 http://www.transitiontherapeutics.com/media/archive.php Accessed January 1, 2013). Lack of the ability to sustain these results was likely due to the ongoing autoimmune attack on the new beta cells generated by therapy. Gastrin alone has been shown to induce beta cell neogenesis from human pancreatic ductal tissue without epidermal growth factor in in vitro studies (Suarez-Pinzon WL et al. JCEM. 2005;90(6):3401-3409).

Type 1 diabetes is an autoimmune disease. Despite evidence that many different immune tolerance agents have successfully reversed diabetes in rodent type 1 models, none have been successful in sustaining insulin independence in man (Ablamunits V et al. Ann NY Acad Sci. 2007;1103:19-32). The distinctions and complexities of islets in man are far different than that of rodents (Levetan CS and Pierce SM. Endocr Pract. 2012 Nov 27:1-36 Epub ahead of print). We hypothesize that in man, both an immune tolerance agent and a beta regeneration agent are required to sustain insulin independence.

Based upon proton-pump inhibitors having been shown to increase plasma gastrin levels up to 10-fold, this clinical trial utilizes the oral proton-pump inhibitor, Lansoprazole. This study will determine the safety and efficacy of Cyclosporine A used with and without Lansoprazole to determine the impact on insulin independence among patients with existing type 1 diabetes.

Cyclosporine A is utilized to protect the new beta cells formed by Lansoprazole. The combination of the two therapies may render reductions in insulin requirements and have a greater impact on sustained insulin independence than previously reported with Cyclosporine A or gastrin alone among type 1 patients.A

This 52-week study consists of two treatment arms designed to assess the safety and efficacy of achieving insulin independence using:

* Oral Lansoprazole/Oral Cyclosporine A
* Oral Placebo/Oral Placebo

It is hypothesized that the combination of oral Cyclosporine A and oral Lansoprazole will safely render significantly more patients with existing type 1 diabetes, insulin independent and may serve as a novel and innovative treatment approach for patients with type 1 diabetes utilizing two FDA-approved therapies.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.