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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01786707
Recruitment Status : Completed
First Posted : February 8, 2013
Results First Posted : April 21, 2014
Last Update Posted : July 2, 2017
Diabetes Research Institute Foundation
Information provided by (Responsible Party):
Rodolfo Alejandro, University of Miami

Tracking Information
First Submitted Date  ICMJE February 5, 2013
First Posted Date  ICMJE February 8, 2013
Results First Submitted Date  ICMJE December 20, 2013
Results First Posted Date  ICMJE April 21, 2014
Last Update Posted Date July 2, 2017
Study Start Date  ICMJE July 2009
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
Number of Participants With a Reduction of HbA1c of >0.5% [ Time Frame: 1 year ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 7, 2013)
The Reduction in HbA1c From Time of Randomization to 1 Year After Intervention. [ Time Frame: 1 year ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2017)
The Number of Subjects With a Reduction of >1% in HbA1c [ Time Frame: at 1 year ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 7, 2013)
The Proportion of Subjects With a Reduction of >1% in HbA1c [ Time Frame: at 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Autologous Stem Cell and Hyperbaric Oxygen Therapy in Type 2 Diabetes Mellitus
Official Title  ICMJE Phase 2 Study of Autologous Stem Cell and Hyperbaric Oxygen Therapy in Type 2 Diabetes Mellitus
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Type 2 Diabetes Mellitus
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • Experimental: Autologous SC and HOT
    Autologous stem cells and hyperbaric oxygen therapy
    • Biological: Autologous stem cells
    • Other: Hyperbaric oxygen therapy
    • Drug: Insulin
    • Drug: Metformin
  • Active Comparator: Control group
    Patients in a control group will continue with standard medical treatment (Insulin and Metformin)
    • Drug: Insulin
    • Drug: Metformin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 18, 2014)
Original Actual Enrollment  ICMJE
 (submitted: February 7, 2013)
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date March 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 45 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01786707
Other Study ID Numbers  ICMJE 20070881
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Rodolfo Alejandro, University of Miami
Study Sponsor  ICMJE Rodolfo Alejandro
Collaborators  ICMJE Diabetes Research Institute Foundation
Investigators  ICMJE
Principal Investigator: Rodolfo Alejandro, MD Diabetes Research Institute, University of Miami Miller School of Medicine
PRS Account University of Miami
Verification Date June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP