A Phase 2/3 interventional study of GnRH, gonadorelin acetate and 0.9% NaCl in Down Syndrome, Cognitive Decline and Alzheimer Disease, Early Onset, sponsored by Nelly Pitteloud. Recruiting at 1 site in Switzerland. Open to participants aged 16 Years to 50 Years. Per ClinicalTrials.gov, last updated 2024-02-12.
Sponsored by Nelly Pitteloud · Phase 2/3, Interventional, and Treatment
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.
438 studies on the registry are indexed under Down Syndrome; 99 are open to participants now.
This study's planned enrollment of 56 is above the median of 37 across 286 interventional studies indexed under Down Syndrome.
Browse Down Syndrome studies →This is the only study on the registry with Nelly Pitteloud as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: GnRH, gonadorelin acetate
Drug: 0.9% NaCl
Drug administered by a subcutaneous pump
Also known as: Lutrelef
Drug administered by a subcutaneous pump
Cognition
Montreal Cognitive Assessment (MoCA) total score ranges between 0 and 30 (cut-off set at 26 for the healthy population) Higher scores reflect better performance.
Time frame: Baseline to end of treatment (Week 24)
Dimensional change card sorting task (DCCS)
change in score of DCCS to assess executive functions
Time frame: baseline to end of treatment (Week 24)
Paired Associated Learning (PAL, part of the CANTAB battery)
change in score of PAL to assess learning
Time frame: baseline to end of treatment (Week 24)
Token test
change in score of Token test to assess verbal comprehension
Time frame: baseline to end of treatment (Week 24)
Corsi block tapping task
change in score to assess visuospatial memory
Time frame: baseline to end of treatment (Week 24)
Litmus non-word-repetition test
change in score of Litmus test to assess phonological abilities
Time frame: baseline to end of treatment (Week 24)
Health-related quality of life SF-12
The health-related quality of life (HRQoL) can be used to measure the effects of healthcare interventions and provide quality-improvement outcomes. The Short Form-12 (SF-12) Health Survey is widely used in measuring HRQoL. SF-12 is a reliable, valid measure in a variety of population groups; it is an equivalent substitute for the SF-36v2 for the summary scales. The response to each of the 12 items is weighted separately by the physical and mental component summary (PCS and MCS) regression coefficients and then calculated to give the SF-12 PCS and MCS scores.
Time frame: baseline to end of treatment (Week 24)
Adaptive behavior (Vineland II) - caregiver questionnaire
change in score of Vineland II (normed assessment tool that assesses adaptive behavior across the areas of communication, activities of daily living, and socialization).
Time frame: baseline to end of treatment (Week 24)
Glycemia
Glucose concentration (mmol/L) is a metabolic parameter.
Time frame: baseline to end of treatment (Week 24)
Insulinemia
Insulin concentration (nmol/L) is a metabolic parameter.
Time frame: baseline to end of treatment (Week 24)
Total cholesterol
Total cholesterol (mmol/L) is a metabolic parameter.
Time frame: baseline to end of treatment (Week 24)
High density lipoprotein (HDL)-cholesterol
HDL-cholesterol (mmol/L) is a metabolic parameter.
Time frame: baseline to end of treatment (Week 24)
Low density lipoprotein (LDL)-cholesterol
LDL-cholesterol (mmol/L) is a metabolic parameter.
Time frame: baseline to end of treatment (Week 24)
Triglycerides
Triglycerides (mmol/L) is a metabolic parameter.
Time frame: baseline to end of treatment (Week 24)
Started Aug 2020 (actual). Primary completion is estimated for Dec 2028, 100 months after the start.
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Studies of the drug tested here: Gonadotropin-Releasing Hormone