Desferal administration to improve the impaired reaction to hypoxia in diabetes (DESIRED) - A randomised, double-blind, placebo-controlled, cross-over study

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

12 Jan 2017 → ongoing

Decision date (initial)

2025-01-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519562-48-00

EudraCT number

2016-003621-41

ClinicalTrials.gov

NCT03085771

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

To investigate whether systemic administration of deferoxamine can improve the response to hypoxic challenge in patients with diabetes mellitus type 1.

Conditions and MedDRA coding

The study will investigate the effect of deferoxamine on the impaired reaction to hypoxia in patients with diabetes mellitus type 1.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patients with diabetes mellitus type 1 with a duration of the disease between 5 and 40 years
2. HbA1c 55-100 mmol/mol
3. Age 18-55
4. Normal ECG result, showing no signs of significant cardiac disorders
5. Contraception: Female subjects must be postmenopausal, surgically sterile, or, if premenopausal (and not surgically sterile), use a highly effective method of contraception during the study and for 30 days after the last visit. Highly effective methods of contraception are considered to be those listed below: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; or progestogen-only hormonal contraception associated with inhibition of ovulation; or intrauterine device; or intrauterine hormonereleasing system; or bilateral tubal occlusion; or vasectomised partner; or sexual abstinence
6. Signed informed consent

Exclusion criteria 22

1. Major cardiovascular complications such as coronary heart disease, unstable or stable angina, myocardial infarction, ventricular XML File Identifier: GVRsEn/+aiS1r4rVgVsURkq36HM= Page 11/21 arrhythmias, and atrial fibrillation in the last 3 months
2. Congestive heart failure (as suggested by anamnesis and by a value of NT-proBNP <155 ng/ml)
3. History of asthma or chronic obstructive pulmonary disease
4. Renal insufficiency (cystatin clearance <60 ml/min)
5. Liver disease (ALAT/ASAT values >2 times the normal levels or INR > 1,2 or albumin levels < 36 g/ l or total bilirubin < 26 micromol/l or gamma GT <2 mikrokat/l)
6. Therapy with β-blockers
7. Severe hypertension (≥180 mmHg systolic or ≥110 mmHg diastolic blood pressure)
8. Proliferative retinopathy
9. Sign for peripheric diabetic neuropathy (decreased/absent sensitivity to 10 g monofilament, vibration, plantar reflex)
10. Definite cardiovascular autonomic dysfunction
11. History of anemia, bleeding gastric ulcer, abundant menstruation
12. Currently smoking
13. History of alcohol or drug abuse
14. Infections that necessitated antibiotic therapy during the last month
15. Malignancy (with the exception of in situ cancer) that has been declared treated within the last 5 years
16. Participant in another ongoing pharmacological study
17. Unwillingness to participate following oral and written information
18. If female: plans to become pregnant, known pregnancy or a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
19. Any concomitant disease or condition that may interfere with the possibility for the subject to comply with or complete the study protocol
20. Subjects with any other severe acute or chronic medical or psychiatric condition that make the subject inappropriate for the study in the judgment of the Investigator
21. Known hypersensitivity to the active substance
22. Treatment with Prochlorperazine

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of Endothelial Precursor Cells in 10 ml blood after intermittent hypoxia exposure

Secondary endpoints 3

1. Changes in the levels of angiogenetic chemokines (SDF-1, EPO, VEGF)
2. Changes in the levels of angiogenetic and hypoxic induced genes (VEGFA, SDF-1, BPNP3, GLUT3, PDK1)
3. Changes in electrophysiological parameters important for the cardiorespiratory response: R-R interval change, the standard deviation of the R-R interval, systolic and diastolic blood pressure, end-tidal carbon dioxide, arterial oxygen saturation, breathing rate, tidal volume, minute ventilation and the ratio between Vt and inspiration time (Vt/Ti), baroreflex sensitivity, arterial function parameters: pulse wave velocity, augmentation index, augmentation index corrected for heart rate (AI75)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Principal Investigator

Public contact point

Organisation

Karolinska University Hospital

Contact name

Principal Investigator

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications