## Protocol Section
### Identification Module
**NCT ID:** NCT06419777

**Acronym:** START 1

**Brief Title:** Strict Versus Permissive Thresholds for Initiation of Pharmacotherapy in Gestational Diabetes

**Official Title:** Strict Versus Permissive Threshold for Initiation of Pharmacotherapy in Gestational Diabetes Mellitus (GDM) With Glucometer Use - A Randomized Control Trial (START1)

#### Organization Study ID Info
**ID:** iRISID-2024-2999
#### Organization
**Class:** OTHER
**Full Name:** Thomas Jefferson University
### Status Module
#### Completion Date
**Date:** 2026-05

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-17

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-14

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-05

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-17
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-09
**Study First Submit QC Date:** 2024-05-14
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** University of Rochester

#### Lead Sponsor

**Class:** OTHER

**Name:** Thomas Jefferson University

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The aim of our study is to compare neonatal and maternal outcomes using different thresholds for the initiation and titration of pharmacotherapy for gestational diabetes (GDM). Our goal is to compare a strict and permissive threshold. The strict threshold is defined as two abnormal values or more over a one-week period (two fasting values elevated, two of the same post prandial values elevated, or 1 fasting and 1 post prandial value elevated), whereas the permissive threshold is defined as 50% of values elevated over 1 week (50% of overall fasting values, 50% of postprandial values, or 50% of overall values).

**Detailed Description:** Pregnancy is a state of insulin resistance to ensure that the growing fetus has ample nutrition. Gestational Diabetes (GDM) develops in pregnant patients with pancreatic dysfunction that leads to impairment of glucose tolerance.

Various studies have examined the benefit of treatment for GDM, including the 2005 Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) and the 2009 Landon et al randomized controlled trials. These studies found that treatment was associated with a significant reduction in newborn complications of perinatal death, shoulder dystocia, large for gestational age infants, cesarean delivery, and birth trauma. The specific threshold value for initiation and up-titration of medical therapy is unknown. Lack of evidence leads to a wide variation in clinical practice of pharmacological initiation and titration for GDM. A systematic review and meta-analysis by Caissutti in 2019 analyzed criteria for initiating pharmacotherapy for GDM and noted the following: 12 of 15 trials initiated pharmacotherapy after 1-2 abnormal values over 1-2 weeks, 2 studies initiated pharmacotherapy after 50% of overall values were abnormal, and 1 study initiated pharmacotherapy after 30% of overall values were abnormal. However, there have been no randomized controlled trials of head-to-head comparison of different thresholds.

The aim of our study is to compare neonatal and maternal outcomes using different thresholds for the initiation and titration of pharmacotherapy for gestational diabetes. Our goal is to compare a strict and relaxed threshold. The strict threshold is defined as two abnormal values or more over a one week period (two fasting values elevated, two of the same post prandial values elevated, or 1 fasting and 1 post prandial value elevated), whereas the relaxed threshold is defined as 50% of values elevated over 1 week (50% of overall fasting values, 50% of postprandial values, or 50% of overall values).

### Conditions Module

**Conditions:**

- Gestational Diabetes

- Pregnancy Related

**Keywords:**

- gestational diabetes

- pregnancy

- insulin

- Initiation of medication

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 430

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** The strict threshold is defined as two abnormal values or more over a one-week period (two fasting values elevated, two of the same post prandial values elevated, or 1 fasting and 1 post prandial value elevated)

**Intervention Names:**

- Drug: Insulin

**Label:** Strict Arm

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** The permissive threshold is defined as 50% of values elevated over 1 week (50% of overall fasting values, 50% of postprandial values, or 50% of overall values).

**Intervention Names:**

- Drug: Insulin

**Label:** Permissive

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Permissive

- Strict Arm

**Description:** Insulin will be used in gestational diabetics to control blood glucose levels

**Name:** Insulin

**Other Names:**

- Lantus

- Lispro

- NPH

- Levemir

- Humalog

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** neonatal composite including the following measures: large for gestational age (LGA) of neonate defined as birth weight \>90th percentile for gestational age using the Fenton growth chart, hypoglycemia o defined as glucose \<40 mg/dL \<48 hours after birth or glucose, hyperbilirubinemia, stillbirth or neonatal death, birth trauma

**Measure:** Neonatal Composite Outcome

**Time Frame:** First 28 days of birth

#### Secondary Outcomes

**Description:** Gestational age at delivery in weeks and days

**Measure:** Neonatal Outcome: Gestational Age of Birth

**Time Frame:** Delivery Time

**Description:** Scoring system provided a standardized assessment for infants after delivery from 0-10

**Measure:** Neonatal Outcome: APGAR Score

**Time Frame:** At 1 minute of life and at 5 min of life

**Description:** Birthweight in grams, Macrosomia (birthweight \>4000g, Small for gestational age (\<10th percentile based on Fenton Growth Charts)

**Measure:** Neonatal Outcome: Birthweight

**Time Frame:** Delivery Time

**Description:** Brachial plexus nerves in neonate are torn, stretched, or compressed at delivery

**Measure:** Neonatal Outcome: Brachial Plexus Injury

**Time Frame:** Delivery Time

**Description:** Breathing difficulties after birth requiring supplemental oxygen, mask, intubation, and/or surfactant

**Measure:** Neonatal Outcome: Respiratory distress

**Time Frame:** Within first 24 hours after delivery

**Description:** Admission to neonatal intensive care unit (NICU)

**Measure:** Neonatal Outcome: Admission to Neonatal intensive Care Unit

**Time Frame:** From delivery to discharge from NICU

**Description:** Maternal episode of hypoglycemia \< 60 mg/dL throughout the pregnancy

**Measure:** Maternal Outcomes: Maternal hypoglycemia

**Time Frame:** Initiation of insulin to delivery

**Description:** An obstetric emergency where the anterior fetal shoulder becomes stuck on the maternal pubic symphysis, delaying the birth of the baby's body.

**Measure:** Maternal Outcomes: Shoulder Dystocia

**Time Frame:** At Delivery

**Description:** 3rd degree and 4th degree perineal injuries

**Measure:** Maternal Outcomes: Obstetric anal sphincter injury (OASIS)

**Time Frame:** At Delivery

**Description:** Vacuum-assisted and Forcep-assisted vaginal Delivery

**Measure:** Maternal Outcomes: Operative Delivery

**Time Frame:** At Delivery

**Description:** Cesarean birth

**Measure:** Maternal Outcomes: Cesarean Delivery

**Time Frame:** At Delivery

**Description:** Defined as cumulative blood loss ≥1000 mL, or bleeding associated with signs/symptoms of hypovolemia within 24 hours of the birth process

**Measure:** Maternal Outcomes: Postpartum hemorrhage

**Time Frame:** Within 24 hours of delivery

**Description:** Hypertensive disorders of pregnancy: gestational hypertension, Preeclampsia without severe features, Pre-eclampsia with severe features, severe range blood pressures defined as (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥110 mmHg), symptoms of central nervous dysfunction, thrombocytopenia with Platelet count \<100,000 platelets/microL, hepatic abnormalities, kidney impairment, and or pulmonary edema

**Measure:** Maternal Outcomes: Hypertensive Disorders of Pregnancy

**Time Frame:** From gestational age of 20 weeks during pregnancy to 6 weeks postpartum

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Live, non-anomalous fetus
* Literacy in English, Spanish, Mandarin, or Arabic
* Patients are also required to provide consent, demonstrate an understanding of the purpose of the study, and agree to the study protocol.

Exclusion Criteria:

* \<18 years at EDD
* pre-existing diabetes or diagnosis of GDM before 24 weeks
* multi-fetal gestation
* known major fetal anomaly
* known allergy to insulin
* chronic maternal corticosteroid use
* diagnosis of GDM based on finger sticks alone
* patients who have contraindication to oral glucose tolerance test
* a primary language other than English, Spanish, Mandarin, or Arabic

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** kxk334@jefferson.edu

**Name:** Kavisha Khanuja, MD

**Phone:** 215-955-5000

**Role:** CONTACT

**Contact 2:**

**Email:** rodney.mclaren@jefferson.edu

**Name:** Rodney McLaren Jr, MD

**Phone:** 215-955-5000

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Rochester

**Country:** United States

**Facility:** University of Rochester Medical Center

**State:** New York

**Zip:** 14642

**Location 2:**

**City:** Philadelphia

**Contacts:**

***Contact 1:***

- **Name:** Kavisha Khanuja, MD

- **Role:** CONTACT

***Contact 2:***

- **Name:** Rodney McLaren, MD

- **Role:** CONTACT

**Country:** United States

**Facility:** Thomas Jefferson University

**State:** Pennsylvania

**Zip:** 19107

### IPD Sharing Statement Module

**IPD Sharing:** NO

### References Module

#### References

**Citation:** Quintanilla Rodriguez BS, Mahdy H. Gestational Diabetes. 2023 Aug 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK545196/

**PMID:** 31424780

**Citation:** Catalano PM, Hauguel-De Mouzon S. Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic? Am J Obstet Gynecol. 2011 Jun;204(6):479-87. doi: 10.1016/j.ajog.2010.11.039. Epub 2011 Feb 2.

**PMID:** 21288502

**Citation:** Gregory EC, Ely DM. Trends and Characteristics in Gestational Diabetes: United States, 2016-2020. Natl Vital Stat Rep. 2022 Jul;71(3):1-15.

**PMID:** 35877134

**Citation:** Metzger BE, Persson B, Lowe LP, Dyer AR, Cruickshank JK, Deerochanawong C, Halliday HL, Hennis AJ, Liley H, Ng PC, Coustan DR, Hadden DR, Hod M, Oats JJ, Trimble ER; HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcome study: neonatal glycemia. Pediatrics. 2010 Dec;126(6):e1545-52. doi: 10.1542/peds.2009-2257. Epub 2010 Nov 15.

**PMID:** 21078733

**Citation:** ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018 Feb;131(2):e49-e64. doi: 10.1097/AOG.0000000000002501.

**PMID:** 29370047

**Citation:** Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005 Jun 16;352(24):2477-86. doi: 10.1056/NEJMoa042973. Epub 2005 Jun 12.

**PMID:** 15951574

**Citation:** Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, Wapner RJ, Varner MW, Rouse DJ, Thorp JM Jr, Sciscione A, Catalano P, Harper M, Saade G, Lain KY, Sorokin Y, Peaceman AM, Tolosa JE, Anderson GB; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009 Oct 1;361(14):1339-48. doi: 10.1056/NEJMoa0902430.

**PMID:** 19797280

**Citation:** Hartling L, Dryden DM, Guthrie A, Muise M, Vandermeer B, Donovan L. Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. Ann Intern Med. 2013 Jul 16;159(2):123-9. doi: 10.7326/0003-4819-159-2-201307160-00661.

**PMID:** 23712381

**Citation:** Davitt C, Flynn KE, Harrison RK, Pan A, Palatnik A. Current practices in gestational diabetes mellitus diagnosis and management in the United States: survey of maternal-fetal medicine specialists. Am J Obstet Gynecol. 2021 Aug;225(2):203-204. doi: 10.1016/j.ajog.2021.04.263. Epub 2021 May 14. No abstract available.

**PMID:** 34000260

**Citation:** Caissutti C, Saccone G, Ciardulli A, Berghella V. Very tight vs. tight control: what should be the criteria for pharmacologic therapy dose adjustment in diabetes in pregnancy? Evidence from randomized controlled trials. Acta Obstet Gynecol Scand. 2018 Mar;97(3):235-247. doi: 10.1111/aogs.13257. Epub 2017 Dec 14.

**PMID:** 29125636

**Citation:** Harrison RK, Cruz M, Wong A, Davitt C, Palatnik A. The timing of initiation of pharmacotherapy for women with gestational diabetes mellitus. BMC Pregnancy Childbirth. 2020 Dec 11;20(1):773. doi: 10.1186/s12884-020-03449-y.

**PMID:** 33308193

**Citation:** Landy HJ, Gomez-Marin O, O'Sullivan MJ. Diagnosing gestational diabetes mellitus: use of a glucose screen without administering the glucose tolerance test. Obstet Gynecol. 1996 Mar;87(3):395-400. doi: 10.1016/0029-7844(95)00460-2.

**PMID:** 8598962

**Citation:** Harper LM, Mele L, Landon MB, Carpenter MW, Ramin SM, Reddy UM, Casey B, Wapner RJ, Varner MW, Thorp JM Jr, Sciscione A, Catalano P, Harper M, Saade G, Caritis SN, Sorokin Y, Peaceman AM, Tolosa JE; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU) Network. Carpenter-Coustan Compared With National Diabetes Data Group Criteria for Diagnosing Gestational Diabetes. Obstet Gynecol. 2016 May;127(5):893-898. doi: 10.1097/AOG.0000000000001383.

**PMID:** 27054932

**Citation:** Blum AK. Insulin Use in Pregnancy: An Update. Diabetes Spectr. 2016 May;29(2):92-7. doi: 10.2337/diaspect.29.2.92. Erratum In: Diabetes Spectr. 2016 Aug;29(3):191.

**PMID:** 27182178

**Citation:** Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr. 2013 Apr 20;13:59. doi: 10.1186/1471-2431-13-59.

**PMID:** 23601190

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000044882

- Term: Glucose Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000004700

- Term: Endocrine System Diseases

- ID: D000011248

- Term: Pregnancy Complications

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M19012

- Name: Diabetes, Gestational

- Relevance: HIGH

- As Found: Gestational Diabetes

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: HIGH

- As Found: Diabetes

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25403

- Name: Glucose Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000016640

- Term: Diabetes, Gestational

- ID: D000003920

- Term: Diabetes Mellitus

### Intervention Browse Module - Ancestors

- ID: D000007004

- Term: Hypoglycemic Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M10365

- Name: Insulin

- Relevance: HIGH

- As Found: Day 1

- ID: M173166

- Name: Insulin, Globin Zinc

- Relevance: LOW

- As Found: Unknown

- ID: M29802

- Name: Insulin Lispro

- Relevance: HIGH

- As Found: Spectroscopy

- ID: M349

- Name: Insulin Detemir

- Relevance: HIGH

- As Found: Military

- ID: M347

- Name: Insulin Glargine

- Relevance: LOW

- As Found: Unknown

- ID: M10054

- Name: Hypoglycemic Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000007328

- Term: Insulin

- ID: D000061268

- Term: Insulin Lispro

- ID: D000069057

- Term: Insulin Detemir

### Misc Info Module

- Version Holder: 2024-05-31
