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

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ClinicalTrials.gov Identifier: NCT01265017
Recruitment Status : Withdrawn (Insufficient funding)
First Posted : December 22, 2010
Last Update Posted : April 18, 2018
Sponsor:
Information provided by (Responsible Party):
Kristin Castorino, DO, Sansum Diabetes Research Institute

Brief Summary:

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 or disease Intervention/treatment Phase
Type 1 Diabetes Drug: Estradiol, medroxyprogesterone, hydrocortisone, GH Drug: Matching placebo Phase 1

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 (Estradiol, medroxyprogesterone, hydrocortisone, GH) 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)

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, 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
Study Start Date : July 2012
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020


Arm Intervention/treatment
Experimental: Active Treatment

interventions include Estradiol, medroxyprogesterone, hydrocortisone, GH as follows

  • 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



Primary Outcome Measures :
  1. stimulated C-peptide response [ Time Frame: 6 weeks ]
    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 :
  1. Clinical, immunologic and hormonal responses [ Time Frame: 6 weeks ]
    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

  2. Insulin requirement [ Time Frame: 6 weeks ]
    Proportion of subjects with a 25% or greater decrease from Baseline in total daily insulin requirement at Week 6



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01265017


Locations
United States, California
Sansum Diabetes Research Institute
Santa Barbara, California, United States, 93105
Sponsors and Collaborators
Sansum Diabetes Research Institute
Investigators
Principal Investigator: Lois Jovanovic, MD Sansum Diabetes Research Institute

Responsible Party: Kristin Castorino, DO, Principal Investigator, Sansum Diabetes Research Institute
ClinicalTrials.gov Identifier: NCT01265017     History of Changes
Other Study ID Numbers: SDRI 2009-06
First Posted: December 22, 2010    Key Record Dates
Last Update Posted: April 18, 2018
Last Verified: April 2018

Keywords provided by Kristin Castorino, DO, Sansum Diabetes Research Institute:
type 1 diabetes
pregnancy
insulin requirement

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