Hydroxychloroquine in Type 2 Diabetes During Pregnancy

Hydroxychloroquine as an Adjunct Therapy in the Management of Type 2 Diabetes in Pregnancy: A Randomised Controlled Trial

The goal of this clinical trial is to compare the use of hydroxychloroquine as an adjunct to the current treatment of pregnant women with Type 2 diabetes mellitus.

The main questions it aims to answer are:

• Does hydroxychloroquine improve the pregnancy outcomes in women with type 2 diabetes during pregnancy?
• Does hydroxychloroquine improve the inflammatory markers in women with type 2 diabetes during pregnancy? Participants will be randomised into the intervention and control group. The control group will be on standard treatment where as the intervention group will receive hydroxychloroquine as an adjunct of standard treatment

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes; Diabetes in Pregnancy
• Intervention / Treatment: Drug: Hydroxychloroquine Oral Tablet

Detailed Description

This is a randomised clinical trial comparing 2 groups i.e type 2 diabetes complicating pregnancies on standard treatment alone which comprises of oral hypoglycaemic agent with or without insulin and those with added hydroxychloroquine 200mg daily. They will be recruited within 14-20 weeks gestation. Randomisation will be done using computer software program. At recruitment, blood is withdrawn to measure glycated haemoglobin (HbA1c), full blood count, fructosamine, Interleukin-6, Interleukin-10 and Tumour Necrosis Factor-alpha. These investigations will be repeated before delivery. Patients will monitor their blood glucose using staggered 7 points which consisting of pre-meals and 1 hour post-meals using their own glucometer. The optimum fasting level is 4-5.3 mmol/l, pre meal and pre bed levels of 4-6 mmol/l and 1 hour post meal level of 4-7.8 mmol/l. All participants are followed up every 2-4 weekly whereby home blood glucose monitoring will be reviewed. Fetal growth will be monitored via serial ultrasound and charted on the fetal growth chart. Patients' care will be done by the research team which consist of obstetrician, endocrinologist and diabetic educator. All patients will have eye assessment by the ophthalmologist prior to commencement of hydroxychloroquine.

All women will be delivered at 38 weeks or earlier if there are other concomitant problems such as fetal growth restriction or poorly controlled diabetes via induction of labour. The details of the delivery for both mother and neonates will be documented. At birth, the offsprings will be seen by the neonatologist who is also in the research team. After delivery, participants will be followed up in research clinic at 6 and 12 months together with the neonate. The height and weight of the infants will be measured in centimeter. Developmental milestones will be assessed according to the developmental milestones chart of Paediatric Protocols for Malaysian Hospitals 4th Edition 2019.

Compliance to hydroxychloroquine will be assessed at each follow up, whereby an indirect method of assessing adherence of participants in the hydroxychloroquine group will be made. Each participant will be asked whether they are still taking the study medication and are required to bring the remaining medication for tablet count. Participants with remaining of more than 20% of the scheduled medications will be considered as non-compliance and treated as drop-out. Participants will also be considered as drop-out when they are lost to follow-up, withdrawal of consent, non-compliance to hydroxychloroquine or a patient becomes ill due to drug adverse effects.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rahana Abdul Rahman, MD; Phone Number: 5964 039145; Email: drrahana@ukm.edu.my

Study Locations

• Malaysia
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • Recruiting
      • Antenatal clinic, UKM Medical Centre
      • Contact: Rahana Abd Rahman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Singleton
• Pregnant women with a confirmed diagnosis of type 2 Diabetes Mellitus

Exclusion Criteria:

• autoimmune disease such as Systemic Lupus Erythematosus or rheumatic disease
• chronic kidney disease
• fetal anomaly
• women on steroid therapy
• diabetic retinopathy
• known thalassaemia or thalassaemia carrier

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard treatment group; Women will receive standard treatment for diabetes such as metformin and insulin.
Experimental: Hydroxychloroquine group; Oral hydroxychloroquine 200mg daily will be prescribed to women in this group from recruitment (14-20 weeks) till delivery, in addition to their standard treatment	Drug: Hydroxychloroquine Oral Tablet; 200mg daily; Other Names: plaquenil

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the serum fructosamine between the two groups	Serum level of fructosamine in nanogram per milliliter	From Day 1 up to 38 weeks of gestation
To compare the serum interleukin-6 between the two groups	Serum level of interleukin-6 in nanogram per milliliter	From Day 1 up to 38 weeks of gestation
To compare the serum interleukin-10 between the two groups	Serum level of interleukin-10 in nanogram per milliliter	From Day 1 up to 38 weeks of gestation
To compare the serum tumour necrosis factor alpha between the two groups	Serum level of tumour necrosis factor alpha in nanogram per milliliter	From Day 1 up to 38 weeks of gestation
To compare the serum glycated haemoglobin (HbA1c) between the two groups	Serum level of glycated haemoglobin (HbA1c) in percentage	From Day 1 up to 38 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the gestational age at delivery between the two groups	Gestational age at delivery in weeks	From recruitment up to 38 weeks of gestation
Type of labour	Onset of labour either spontaneous or induced	From recruitment up to 38 weeks of gestation
Mode of delivery	Method of patient being delivered either vaginal or caesarean section	From recruitment up to 38 weeks of gestation
Postpartum haemorrhage	Total blood loss of more than 500 milliliters for vaginal delivery and 1000 milliliters for caesarean delivery	Immediately from delivery up to 42 days post delivery
Shoulder dystocia	Number of patient who experienced shoulder dystocia at delivery	At delivery up to 24 hours
Appearance, pulse, grimace, activity and respiration score of neonate at 5 minutes	Number of neonates with Apgar score of less than 7 at birth which is bad outcome	At delivery up to 10 minutes after delivery
Number of neonates needing admission into neonatal intensive care unit	Admission of neonate into neonatal intensive care unit at birth	At delivery up to 7 days of life
Obstetric anal sphincter injuries	The number of patients who suffered third or fourth degree perineal tear	Immediately from delivery up to 24 hours
Neonatal birth weight at delivery	Birth weight of the neonate in grams, Neonatal birth weight of more than 90th percentile based on Fenton birth weight chart will be considered as large for gestational age or more than 4000 grams will be considered as macrosomia	At delivery up to 24 hours
Height of the infant	Height or length of the infant measured in centimetres	At six and twelve months of age after delivery
Weight of the infant	Weight of the infant measured in grams	At six and twelve months of age after delivery
Hospital admission	Numbers of infants required hospital admission	From day 7 of life up to twelve months of age

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Investigators: Principal Investigator: Rahana Abd Rahman, UKM

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: January 23, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): June 12, 2025
• Last Update Submitted That Met QC Criteria: June 9, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: diabetes; pregnancy; hydroxychloroquine
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Female Urogenital Diseases and Pregnancy Complications; Metabolic Diseases; Pregnancy Complications; Glucose Metabolism Disorders; Diabetes, Gestational; Diabetes Mellitus, Type 2; Diabetes Mellitus; Pregnancy in Diabetics; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimalarials; Antiprotozoal Agents; Antiparasitic Agents; Hydroxychloroquine
• Other Study ID Numbers: JEP-2023-866

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No