NCT04390646 GnRH Therapy on Cognition in Down Syndrome
| NCT ID | NCT04390646 |
| Status | Recruiting |
| Phase | Phase 2, Phase 3 |
| Sponsor | Nelly Pitteloud |
| Condition | Down Syndrome |
| Study Type | INTERVENTIONAL |
| Enrollment | 56 participants |
| Start Date | 2020-08-27 |
| Primary Completion | 2028-12 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
In Phase 2, researchers evaluate early signs of effectiveness. You may be randomized to receive the active treatment or a comparator. Monitoring continues closely.
This trial targets 56 participants in total. It began in 2020-08-27 with a primary completion date of 2028-12.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
Down syndrome (DS) is the most common chromosomal disorder; with the increasing life expectancy, about 80% of DS adults reach age 65 years old. Early Alzheimer's disease (AD) is the most common cause of death within this population. DS individuals already show AD neuropathology by the age of 30, while it becomes clinically recognized in their late forties. DS subjects also exhibit olfaction defects in adulthood. To date, there is no treatment available for the cognitive or olfactory defects in DS. The development of an effective treatment targeting cognitive dysfunction in DS adolescents/adults would be warranted. GnRH, a decapeptide secreted by hypothalamic neurons is the pilot light of reproduction in all mammals. Pulsatile GnRH acts on the gonadotrophs via the GnRH receptor (GNRHR) in the pituitary gland to stimulate LH and FSH, which themselves will act on the gonads to produce gametes and steroids. However, GNRHR are also expressed in cerebral cortex, hippocampus, amygdala, habenula, olfactory structures, and adrenal gland, suggesting that GnRH may have a role beyond reproduction. Recently, GnRH has been shown to be involved in the process of ageing and lifespan control. Notably, in murine models, GnRH acts as an anti-ageing factor, independent of sex hormones. While ageing is characterized by hypothalamic inflammation and diminished neurogenesis, particularly in the hypothalamus and the hippocampus, GnRH was able to promote adult neurogenesis. The regulation of GnRH secretion is complex and involves hormonal, neuronal input, and environmental factors. Prévot et al. recently explored cognition within the Ts65Dn model and showed an age-dependent loss of the ability to recognize new objects. Also, these mice exhibit defects in olfaction. Given the role of GnRH in anti-aging mice model, pulsatile GnRH or continuous GnRH infusion (leading to desensitization of the GNRHR) were given to the Ts65Dn mice for two weeks. Amazingly, pulsatile but not continuous GnRH therapy was able to recover cognitive and olfaction defects.
Eligibility Criteria
Inclusion Criteria: * Diagnosis of trisomy 21 * Verbal expression (ability to follow the procedures of the study) * Consent to a non-hormonal contraception during the whole duration of the study For women: intra-uterine device with copper, a prior tubal ligation or condoms for the partner For men: condoms or vasectomy Exclusion Criteria: * Acute illness (clinical or biochemical findings suggesting acute illness/hospitalization) * Chronic alcohol abuse, illicit drug use, anabolic steroid abuse, psychotropic drugs reported by caregivers * Taking medication that modifies hormones: spironolactone, ketoconazole, anticoagulants, corticosteroids, ACTH hormone, psychotropics, including antidepressants, antipsychotics and anticonvulsants. * Known pituitary adenoma and other hormone-dependent tumours * Participation in another clinical study * Intention to become a parent during the course of the study * Females: ovarian cysts, non-hypothalamic anovulation (i.e. polycystic ovary syndrome), pregnancy or lactation * Males: hematocrit \> 54% * Contraindications for MRI (e.g. pacemaker, metal clips,etc) * Participant or his/her legal representative do not want to be informed in case of incidental findings
Contact & Investigator
Nelly Pitteloud, MD
PRINCIPAL INVESTIGATOR
Endocrinology, Metabolism, Diabetology (CHUV)
Frequently Asked Questions
Who can join the NCT04390646 clinical trial?
This trial is open to participants of all sexes, aged 16 Years or older, up to 50 Years, studying Down Syndrome. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT04390646 trial and what does that mean for participants?
Phase 2 trials evaluate whether the treatment shows signs of effectiveness while continuing to monitor safety. More participants are enrolled than in Phase 1 to help refine the treatment protocol.
Is NCT04390646 currently recruiting?
Yes, NCT04390646 is actively recruiting participants. Contact the research team at pulseup@chuv.ch for enrollment information.
Where is the NCT04390646 trial being conducted?
This trial is being conducted at Lausanne, Switzerland.
Who is sponsoring the NCT04390646 clinical trial?
NCT04390646 is sponsored by Nelly Pitteloud. The principal investigator is Nelly Pitteloud, MD at Endocrinology, Metabolism, Diabetology (CHUV). The trial plans to enroll 56 participants.