Aralast NP in Islet Transplant

NCT02520076 | Completed Phase 1 DMC

• 1 other identifier: Pro00047923
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Islet transplantation is a relatively new procedure used in people with difficult to control Type 1 diabetes. Insulin producing cells (islets) are isolated from a pancreas donated by the next of kin of a person who is brain dead. After the cells are prepared, the islets are transplanted into the recipient's liver and produce insulin. Patients who receive an islet transplant take medication that suppresses their immune system and prevent rejection of the islet tissue. The investigators have also learned that there is general inflammation at the time of the transplant that is not fully controlled with our standard medications. The investigators believe this inflammation may cause some islet cell death around the time of transplant. Due to this islet death around the time of transplant, most recipients need 2 or 3 separate transplant procedures. The investigators are studying the use of Alpha-1 Antitrypsin (AAT) in islet transplant to decrease the amount of cell death caused by general inflammation. In this study, the investigators hope to decrease the need for more than one transplant procedure by controlling inflammation, before and after transplant, with Alpha-1 Antitrypsin (Aralast NP). Alpha-1 Antitrypsin is a protein made in healthy humans that helps to prevent tissue damage during times of inflammation. Alpha-1 Antitrypsin is obtained from healthy plasma donors. There have been studies in Islet Transplant in monkeys using this medication and it has shown to protect the islets from inflammation. This study involves using Alpha-1 Antitrypsin in addition to our current Standard of Care medications used in Islet Transplant.

Conditions

Type 1 Diabetes Mellitus

Keywords

Islet Transplantation

Outcome Measures

Primary Outcomes (1)

• To demonstrate AAT efficacy in preventing non-immunologic loss of transplanted islet mass in a single-donor islet transplant.

  Insulin independence at day 90 post-transplant (initial, single-donor transplant)

  Day 90 post-transplant

Secondary Outcomes (4)

• To demonstrate safety of AAT during islet isolation and culture

  Day -1 pre-transplant

• To demonstrate efficacy of AAT to improve islet isolation quantity and quality

  Day -1 pre-transplant

• To demonstrate safety of AAT in islet transplantation.

  Year 1 post-transplant

• To demonstrate AAT efficacy in the prevention of long-term metabolic burn-out.

  Year 1 post-transplant

Study Arms (1)

AAT treated group

EXPERIMENTAL

Study subjects will receive Alpha-1 Antitrypsin (AAT) study drug intravenously in 4 doses over 15 days around the time of their transplant. The islets will also be prepared in a solution of AAT.

Drug: Alpha-1 Antitrypsin

Interventions

Alpha-1 Antitrypsin DRUG

Subjects will receive their islets treated with Aralast NP during islet isolation process. Subjects will receive Aralast NP at a dose of 120 mg/kg (at an infusion rate of 0.2 mL/kg/min or less), dependent on patient tolerance, based on Day -1 admission weight and dose rounded to the nearest 20 mg) at the following time points: * Pre-transplant Day -1 * Post-transplant Day 3 * Post-transplant Day 7 * Post-transplant Day 14

AAT treated group

Eligibility Criteria

• Age: 18 Years - 68 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be eligible the participant must have had Type 1 Diabetes Mellitus (T1DM) for more than 5 years, complicated by at least 1 of the following situations that persist despite intensive insulin management efforts:
• Reduced awareness of hypoglycemia, as defined by the absence of adequate autonomic symptoms at plasma glucose levels \< 3.0 mmol/L, indicated by, 1 or more episodes of severe hypoglycemia requiring third party assistance within 12 months, a Clarke score ≥4, HYPO score ≥1,000, lability index (LI) ≥400 or combined HYPO/LI \>400/\>300.
• Metabolic instability, characterized by erratic blood glucose levels that interfere with daily activities and or 1 or more hospital visits for diabetic ketoacidosis over the last 12 months.
• Participants must be capable of understanding the purpose and risks of the study and must sign a statement of informed consent.

You may not qualify if:

• Hypersensitivity to Aralast NP, history of immunoglobulin A (IgA) deficiency, or assessed low IgA (\< 0.70 g/L).
• Severe co-existing cardiac disease, characterized by any one of these conditions: (a) recent (within the past 6months) myocardial infarction; (b) left ventricular ejection fraction \<30%; or (c) evidence of ischemia on functional cardiac exam.
• Active alcohol or substance abuse, to include cigarette smoking (must be abstinent for 6 months prior to listing for transplant).
• Psychiatric disorder making the subject not a suitable candidate for transplantation, (e.g., schizophrenia, bipolar disorder, or major depression that is unstable or uncontrolled on current medication).
• History of non-adherence to prescribed regimens.
• Active infection including Hepatitis C, Hepatitis B, HIV, or tuberculosis (TB) (subjects with a positive purified protein derivative (PPD) performed within one year of enrollment, and no history of adequate chemoprophylaxis).
• Any history of, or current malignancies except squamous or basal skin cancer.
• BMI \> 35 kg/m2 at screening visit.
• Age less than 18 or greater than 68 years.
• Measured glomerular filtration rate \<60 mL/min/1.73 m2.
• Presence or history of macroalbuminuria (\>300 mg/g creatinine).
• Clinical suspicion of nephritic (hematuria, active urinary sediment) or rapidly progressing renal impairment (e.g. Increase in serum creatinine of 25% within the last 3-6 months).
• Baseline Hb \< 105 g/L in women, or \< 120 g/L in men.
• Baseline screening liver function tests (LFT) outside of normal range, with the exception of uncomplicated Gilbert's Syndrome. An initial LFT panel with any values \>1.5 times the upper limit of normal (ULN) will exclude a patient without a re-test; a re-test for any values between ULN and 1.5 times ULN should be made, and if the values remain elevated above normal limits, the patient will be excluded.
• Untreated proliferative retinopathy.

Sponsors & Collaborators

• University of Alberta: lead
• Shire: collaborator

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G 2C8, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

alpha 1-Antitrypsin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Study Officials

• James Shapiro, MD, PhD

  University of Alberta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2015
• First Posted: August 11, 2015
• Study Start: August 1, 2015
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: May 24, 2022

Record last verified: 2019-10

Locations

CA (1)