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

NCT01265017 | Withdrawn Phase 1

• 1 other identifier: SDRI 2009-06
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

Type 1 Diabetes

Keywords

type 1 diabetes; pregnancy; insulin requirement

Outcome Measures

Primary Outcomes (1)

• 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

  6 weeks

Secondary Outcomes (2)

• Clinical, immunologic and hormonal responses

  6 weeks

• Insulin requirement

  6 weeks

Study Arms (2)

Active Treatment

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Matching placebo

Interventions

Estradiol, medroxyprogesterone, hydrocortisone, GH DRUG

* 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,

Also known as: estradiol,medroxyprogesterone,hydrocortisone,growth hormone

Active Treatment

Matching placebo DRUG

matching placebo

Also known as: inert pills

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sansum Diabetes Research Institute: lead

Study Sites (1)

Sansum Diabetes Research Institute

Santa Barbara, California, 93105, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Estradiol; Medroxyprogesterone; Hydrocortisone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hydroxyprogesterones; Progesterone; Pregnenediones; Pregnenes; Pregnanes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; 17-Hydroxycorticosteroids

Study Officials

• Lois Jovanovic, MD

  Sansum Diabetes Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 20, 2010
• First Posted: December 22, 2010
• Study Start: July 1, 2012
• Primary Completion: June 1, 2020
• Study Completion: June 1, 2020
• Last Updated: April 18, 2018

Record last verified: 2018-04

Locations

US (1)