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Role of Pregnancy Related Hormones in Lowering the Insulin Requirement in Pregnant Women With Type 1 Diabetes

This study is not yet open for participant recruitment.
Verified June 2012 by Sansum Diabetes Research Institute
Sponsor:
Information provided by (Responsible Party):
Lois Jovanovic, MD, Sansum Diabetes Research Institute
ClinicalTrials.gov Identifier:
NCT01265017
First received: December 20, 2010
Last updated: June 5, 2012
Last verified: June 2012
History of Changes
  Purpose

This is a randomized, double-masked, placebo-controlled, single-center study to evaluate stimulated C-peptide secretion after exogenous administration of mild immunosuppression and growth-promoting factors to women with preexisting T1DM who had a decline in insulin requirement or had detectable C-peptide during a previous pregnancy. Fifteen subjects will be enrolled and randomly assigned in a 2:1 ratio to either active treatment or placebo in a parallel group design.

Participation for individual subjects will consist of an initial Screening Visit, a 2-week baseline period, a Baseline Visit, visits at week 2 and 4 of the treatment period, a visit at the end of the treatment period (week 6), and a follow-up visit 2 weeks after study treatment discontinuation.

Subjects will receive either active treatment or matching placebo of estradiol 1 mg every 8 hours; medroxyprogesterone 2.5 mg every 24 hours; hydrocortisone 2.5 mg every morning, 1.25 mg every afternoon, and 1.25 mg at bedtime each night; and growth hormone 2 mg once a day).


Condition Intervention Phase
Type 1 Diabetes
 Drug: Estradiol, medroxyprogesterone, hydrocortisone, GH
Drug: Matching placebo
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Single-center, Double-masked, Placebo-controlled Parallel-group Study of Pregnancy-related Hormones Estradiol and Medroxyprogesterone, in Conjunction With Hydrocortisone and Growth Hormone to Stimulate C-peptide Secretion in Women With T1DM

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Sansum Diabetes Research Institute:

Primary Outcome Measures:
  • stimulated C-peptide response [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The primary efficacy endpoint is the Week 6 change from Baseline in stimulated C peptide response. It will be modeled as a function of treatment group and baseline stimulated C peptide using an analysis of covariance model. The assessment at the Screening Visit will serve as the baseline assessment in computing the C peptide change from baseline endpoint


Secondary Outcome Measures:
  • Clinical, immunologic and hormonal responses [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    The following secondary efficacy endpoint will be summarized descriptively and graphically by treatment group to which subjects were randomized: Week 6 changes from Baseline in the following: HbA1c, Total daily insulin requirement, IAA, GADA, IA-2A, ICA (pending the availability of sample processing, ZnT8A (pending the availability of sample processing), IGF-1, Prolactin, Growth hormone, Cortisol

  • Insulin requirement [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    Proportion of subjects with a 25% or greater decrease from Baseline in total daily insulin requirement at Week 6


Estimated Enrollment: 15
Study Start Date: July 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Active Treatment
  • Estradiol 1mg every 8 hours administered orally
  • Medroxyprogesterone 2.5 mg every 24 hours administered orally
  • Hydrocortisone 2.5 mg every morning, 1.25 mg every afternoon, and 1.25 mg at bedtime administered orally
  • Growth hormone 2 mg once a day administered by subcutaneous injection
 Drug: Estradiol, medroxyprogesterone, hydrocortisone, GH
  • Estradiol 1mg every 8 hours administered orally
  • Medroxyprogesterone 2.5 mg every 24 hours administered orally
  • Hydrocortisone 2.5 mg every morning, 1.25 mg every afternoon, and 1.25 mg at bedtime administered orally
  • Growth hormone 2 mg once a day administered by subcutaneous injection,
Other Name: estradiol,medroxyprogesterone,hydrocortisone,growth hormone
Placebo Comparator: Placebo
Matching placebo
 Drug: Matching placebo
matching placebo
Other Name: inert pills

Detailed Description:

The primary objective of this study is to determine whether women with preexisting T1DM who showed a decline in insulin requirement, defined as a decrease in insulin requirement of 25% or more, or a decrease deemed to be clinically significant by the investigator, with no other medically determined reason, or who had detectable C-peptide during a previous pregnancy will show a change in stimulated C peptide response when not pregnant and treated with exogenous pregnancy-related hormones and growth factors for 6 weeks.

The secondary objectives of this study are as follows:

  • Determine whether the study treatment leads to a change in T1DM autoantibodies between Baseline and Week 6
  • Determine the percentage of subjects experiencing a clinically significant decline in total daily insulin requirement at Week 6, defined as a 25% decrease from Baseline
  • Descriptively evaluate the association between serum levels of growth hormone, cortisol, and prolactin and changes in C-peptide levels
  • Evaluate the safety of administration of the study treatments compared with placebo, as measured by blood pressure, pulse, weight change, blood glucose, and adverse events (AEs)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Female aged 18 years or older with T1DM and a documented history of at least one of the following:
  • Decrease in insulin requirement with no other medically determined reason
  • Detectable C-peptide
  • Free of systemic corticosteroid use within 3 months before study entry.
  • Stable weight (±10%)
  • Stable diet and exercise
  • Stable insulin requirement (<20% variability in insulin does in the 2 weeks prior to screening)Normal renal function as measured by an estimated glomerular filtration rate (simple MDRD)
  • Negative pregnancy test and not planning to become pregnant during the study period. The subject must be willing to use an effective nonhormonal method of birth control during the study.
  • Able to provide written informed consent.

Exclusion Criteria:

  • Diagnosis of type 2 diabetes.
  • Abnormal thyroid function (thyroid-stimulating hormone [TSH] and free thyroxine [FT4] test results) defined as TSH <0.4mIU/L or TSH>4.5mIU/L or Free T4 <0.6ng/dL or Free T4>1.6ng/dL.
  • Abnormal renal function, as defined by serum creatinine greater than 1.2 mg/dL
  • Any medical condition that, in the opinion of the investigator, yields the subject not suitable for study participation, including history of stroke, cancer, hypercoagulable problems, risk for deep vein thrombosis, and other unstable hormonal conditions, or Addison's disease or growth hormone deficiency.
  • Currently treated with systemic steroids, hydrocortisone, growth hormone, or immunomodulatory medications
  • Currently lactating.
  • Pregnant within the last 9 months.
  • Menopausal
  • Taking hormonal therapy
  • Known hypersensitivity to any of the medications used in this study or any component of the formulation.
  • Known eating disorder
  • History of phlebitis
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01265017

Contacts
Contact: Lois Jovanovic, MD 805-682-7638 ext 227 ljovanovic@sansum.org
Contact: Howard Zisser, MD 805-682-7638 ext 255 hzisser@sansum.org

Locations
United States, California
Sansum Diabetes Research Institute Not yet recruiting
Santa Barbara, California, United States, 93105
Contact: Lois Jovanovic, MD     805-682-7638 ext 252     ljovanovic@sansum.org    
Contact: Alison O Wollitzer, PhD     805-682-7638 ext 252     awollitzer@sansum.org    
Principal Investigator: Lois Jovanovic, MD            
Sponsors and Collaborators
Sansum Diabetes Research Institute
Investigators
Principal Investigator: Lois Jovanovic, MD Sansum Diabetes Research Institute
  More Information

No publications provided

Responsible Party: Lois Jovanovic, MD, Chief Scientific Officer, Sansum Diabetes Research Institute
ClinicalTrials.gov Identifier: NCT01265017     History of Changes
Other Study ID Numbers: SDRI 2009-06
Study First Received: December 20, 2010
Last Updated: June 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Sansum Diabetes Research Institute:
type 1 diabetes
pregnancy
insulin requirement

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Estradiol
Polyestradiol phosphate
Hormones
Estradiol valerate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Medroxyprogesterone
Medroxyprogesterone Acetate
 Cortisol succinate
Hydrocortisone acetate
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone
Hydrocortisone-17-butyrate
Estrogens
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Contraceptive Agents
Reproductive Control Agents
Therapeutic Uses
Contraceptive Agents, Female
Anti-Inflammatory Agents
Dermatologic Agents

ClinicalTrials.gov processed this record on May 23, 2013