Autologous Stem Cell and Hyperbaric Oxygen Therapy in Type 2 Diabetes Mellitus (HOT)

Phase 2 Study of Autologous Stem Cell and Hyperbaric Oxygen Therapy in Type 2 Diabetes Mellitus

A prospective, open labeled, randomized controlled clinical trial comparing the benefit of both hyperbaric oxygen therapy and intrapancreatic stem cell infusion to standard medical treatment alone for type 2 diabetes mellitus. Subjects will receive standard medical treatment (SMT) with insulin and metformin for 4 months (evaluation phase). Then they will be randomized into either the intervention group or the control group:

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Biological: Autologous stem cells; Other: Hyperbaric oxygen therapy; Drug: Insulin; Drug: Metformin

Detailed Description

This is a phase I/II, prospective, randomized case controlled study in patients with Type 2 Diabetes Mellitus (T2DM) that seeks to investigate whether the combination of intrapancreatic Autologous Stem Cell infusion (ASC) and Hyperbaric Oxygen treatment (HBO) can improve glycemic control and pancreatic function in T2DM patients compared to controls receiving standard medical treatment (SMT) with metformin and insulin alone.

New therapies that lead to stopping ß-cell damage and possible ß-cell regeneration may decrease the incidence and progression of T2DM chronic complications and together with achievable life style changes may improve general health and quality of life of T2DM patients. Preliminary data from a pilot study involving 25 subjects with T2DM that underwent a combined treatment using ASC+HBO showed a significant progressive and consistent reduction in plasma glucose and HbA1c with an increase in C-peptide in conjunction with a decrease in the number and dose of oral agents and/or insulin. These encouraging preliminary results require confirmation in a controlled, randomized prospective trial.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • Diabetes Research Institute, University of Miami Miller School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female patients age 45 to 65 years of age.
2. Ability to provide written informed consent.
3. Mentally stable and able to comply with the procedures of the study protocol.
4. Clinical history compatible with type 2 diabetes as defined by the Expert Committee on the Diagnosis and classification of Diabetes Mellitus.
5. Onset of Type 2 DM disease at 40 years of age.
6. T2DM duration: 2-15 years at the time of enrollment.
7. Basal C-peptide: 0.3 ng/mL
8. HbA1c of 7.5-12.5% before standard medical therapy. Patients must have been treated with SMT for minimum of 4 months prior to randomization. Insulin and metformin doses should be stable over the 3 months prior to randomization.
9. HbA1c: 7.5-9.5% at time of randomization.
10. Total insulin daily dose at baseline and at randomization <100 units/day.

Exclusion Criteria:

1. BMI >40 kg/m2.
2. Insulin requirements of >100 U/day, and HbA1c >9.5%
3. C-reactive protein >10.00
4. Uncontrolled blood pressure: Systolic Blood Pressure >140 mmHg or Diastolic Blood Pressure >80 mmHg Evidence of renal dysfunction, serum creatinine > 1.5 mg/dl (males) and 1.4 mg/dl (females)
5. Proteinuria >300 mg/day
6. History or EKG evidence of myocardial infarction or any degree of heart failure
7. Female participants: Positive pregnancy test, presently breast-feeding, or unwillingness to use effective contraceptive measures for the duration of the study. Male participants: intent to procreate 3 months before or after the intervention or unwillingness to use effective measures of contraception.
8. Active infection including hepatitis B, hepatitis C, HIV, or Tuberculosis. Positive tests are acceptable only if associated with a history of previous vaccination in the absence of any sign of active infection.
9. Known active alcohol or substance abuse including cigarette/cigar smoking
10. Baseline Hgb below the lower limits of normal at the local laboratory; lymphopenia (<1,000/L), neutropenia (<1,500/L), or thrombocytopenia (platelets <100,000/L).
11. A history of Factor V deficiency or other coagulopathy defined by International normalized ratio (INR) >1.5, Partial thromboplastin time (PTT) >40, Prothrombin time (PT) >15.
12. Acute or chronic pancreatitis.
13. Symptomatic peptic ulcer disease.
14. Hyperlipidemia despite medical therapy
15. Receiving treatment for a medical condition requiring chronic use of systemic corticosteroids in the past six months.
16. Symptomatic cholecystolithiasis.
17. Use of any investigational agents within 4 weeks of enrollment.
18. Admission to hospital for any reason in the 14 days prior to enrollment.
19. History or presence of active proliferative diabetic retinopathy or macular edema.
20. Any malignancy.
21. Hepatic enzyme levels upper normal limits.
22. Total bilirubin upper normal limits unless secondary to known benign condition.
23. Abdominal aortic aneurysm.
24. History of cerebro-vascular accident.
25. Any patient with acute or subacute decompensation from diabetes.
26. Any acute or chronic infectious condition that in the criteria of the investigator would be a risk for the patient.
27. Hypoproteinemia, cachexia or terminal states; history of anorexia/bulimia; respiratory insufficiency; history of chronic sinusitis (sinusitis lasting more than 8 weeks in the past year) or recurrent acute sinusitis (sinusitis lasting more than 4 weeks more than four times in the past year.
28. Any contraindication to hyperbaric oxygen treatment.
29. Subjects treated with any medication that could interfere with the outcome of the study.
30. Subjects positive for auto-antibodies
31. History of Cushing syndrome (endogenous or iatrogenic).
32. History of allergy to iodine or iodinated materials.
33. Abnormal thyroid function
34. Any medical condition that, in the opinion of the investigator, will interfere with the safe completion of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous SC and HOT; Autologous stem cells and hyperbaric oxygen therapy	Biological: Autologous stem cells; Pancreatic artery infusion of Autologous Stem cells.; Other: Hyperbaric oxygen therapy; Drug: Insulin; Insulin dose as per clinical management; Drug: Metformin; Metformin dose as tolerated
Active Comparator: Control group; Patients in a control group will continue with standard medical treatment (Insulin and Metformin)	Drug: Insulin; Insulin dose as per clinical management; Drug: Metformin; Metformin dose as tolerated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With a Reduction of HbA1c of >0.5%	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
The Number of Subjects With a Reduction of >1% in HbA1c	at 1 year

Collaborators and Investigators

• Sponsor: Rodolfo Alejandro
• Collaborators: Diabetes Research Institute Foundation
• Investigators: Principal Investigator: Rodolfo Alejandro, MD, Diabetes Research Institute, University of Miami Miller School of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: February 5, 2013
• First Submitted That Met QC Criteria: February 7, 2013
• First Posted (Estimate): February 8, 2013

Study Record Updates

• Last Update Posted (Actual): July 2, 2017
• Last Update Submitted That Met QC Criteria: June 29, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Type 2 Diabetes Mellitus; Hyperbaric oxygen therapy (HOT); Autologous Bone Marrow-Derived Buffy Coat; Stem cells (SC)
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: 20070881

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO