Type 2 Diabetes Mellitus
Conditions
Keywords
Type 2 Diabetes Mellitus, Hyperbaric oxygen therapy (HOT), Autologous Bone Marrow-Derived Buffy Coat, Stem cells (SC)
Brief summary
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:
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.
Interventions
BIOLOGICALAutologous stem cells
Pancreatic artery infusion of Autologous Stem cells.
OTHERHyperbaric oxygen therapy
DRUGInsulin
Insulin dose as per clinical management
DRUGMetformin
Metformin dose as tolerated
Sponsors
Diabetes Research Institute Foundation
Rodolfo Alejandro
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With a Reduction of HbA1c of >0.5% | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| The Number of Subjects With a Reduction of >1% in HbA1c | at 1 year |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Autologous SC and HOT Autologous stem cells and hyperbaric oxygen therapy
Autologous stem cells and hyperbaric oxygen therapy: Subjects will receive standard medical treatment (SMT) with insulin and metformin for 4 months. Then they will be randomized to either control or intervention groups. HOT and SC group: combination of HOT therapy and intrapancreatic autologous SC infusion in addition to SMT. | 1 |
| Control Group Patients in a control group will continue with standard medical treatment (SMT) | 1 |
| Total | 2 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Autologous SC and HOT | Control Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 1 | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 | 0 / 1 |
Outcome results
Primary
Number of Participants With a Reduction of HbA1c of >0.5%
Time frame: 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Autologous SC and HOT | Number of Participants With a Reduction of HbA1c of >0.5% | 0 Participants |
| Control Group | Number of Participants With a Reduction of HbA1c of >0.5% | 0 Participants |
Secondary
The Number of Subjects With a Reduction of >1% in HbA1c
Time frame: at 1 year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Autologous SC and HOT | The Number of Subjects With a Reduction of >1% in HbA1c | 0 Participants |
| Control Group | The Number of Subjects With a Reduction of >1% in HbA1c | 0 Participants |