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

Primary Purpose

Type 1 Diabetes

Status

Withdrawn

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Estradiol, medroxyprogesterone, hydrocortisone, GH

Matching placebo

About this trial

This is an interventional basic science trial for Type 1 Diabetes focused on measuring type 1 diabetes, pregnancy, insulin requirement

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

Sansum Diabetes Research Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Active Treatment

Placebo

Arm Description

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

Matching placebo

Outcomes

Primary Outcome Measures

stimulated C-peptide response

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

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

Proportion of subjects with a 25% or greater decrease from Baseline in total daily insulin requirement at Week 6

Full Information

NCT ID

NCT01265017

First Posted

December 20, 2010

Last Updated

April 16, 2018

Sponsor

Sansum Diabetes Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT01265017

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

April 2018

Overall Recruitment Status

Withdrawn

Why Stopped

Insufficient funding

Study Start Date

July 2012 (undefined)

Primary Completion Date

June 2020 (Anticipated)

Study Completion Date

June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sansum Diabetes Research Institute

4. Oversight

Data Monitoring Committee

5. Study Description

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).

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)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes

Keywords

type 1 diabetes, pregnancy, insulin requirement

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active Treatment

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Matching placebo

Intervention Type

Drug

Intervention Name(s)

Estradiol, medroxyprogesterone, hydrocortisone, GH

Other Intervention Name(s)

estradiol,medroxyprogesterone,hydrocortisone,growth hormone

Intervention Description

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,

Intervention Type

Drug

Intervention Name(s)

Matching placebo

Other Intervention Name(s)

inert pills

Intervention Description

matching placebo

Primary Outcome Measure Information:

Title

stimulated C-peptide response

Description

Time Frame

6 weeks

Secondary Outcome Measure Information:

Title

Clinical, immunologic and hormonal responses

Description

Time Frame

6 weeks

Title

Insulin requirement

Description

Proportion of subjects with a 25% or greater decrease from Baseline in total daily insulin requirement at Week 6

Time Frame

6 weeks

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Lois Jovanovic, MD

Organizational Affiliation

Sansum Diabetes Research Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sansum Diabetes Research Institute

City

Santa Barbara

State/Province

California

ZIP/Postal Code

93105

Country

United States

12. IPD Sharing Statement

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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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