Pregnenolone Sulfate an Early Marker of the Memory Loss in Alzheimer's Disease

Alzheimer Disease Clinical Trial

— STERMEM  

Official title:

Neuroactive Steroids and Cognition in Humans: Pregnenolone Sulfate an Early Marker of the Memory Loss Associated With Alzheimer's Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00912886
• Other study ID #: P071237
• Status: Completed
• Phase: N/A
• First received: June 2, 2009
• Last updated: April 10, 2013
• Start date: September 2009
• Est. completion date: September 2011

Study information

• Verified date: April 2013
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Observational

Clinical Trial Summary

The steroid pregnenolone sulfate (PREGS) may be one of the factors responsible for the memory decline related to normal aging or associated with Alzheimer's disease (AD). The purpose of this study is to determine whether plasma levels of PREGS are decreased patients with at mild to moderate AD compared with AD-free control subjects matched for gender and age and to see whether they are inversely correlated with the severity of memory deficits in AD patients. The hypothesis is that blood levels of PREGS are decreased with advanced age and with the stage of AD that would be positively correlated with memory deficits. Therefore PREGS could be considered as an early marker of the memory deficits in AD.

Description:

PREGS is a derivative of pregnenolone which the obligatory precursor of all steroid hormones originating from the gonads and adrenal glands. In rodents, PREGS has been demonstrated to improve memory performance in various behavioural tests. In humans, PREGS is one the most abundant circulating steroids. There are some indications about its decrease in blood during aging, and in brain samples from aged patients with AD, low concentrations of PREGS have been correlated with high levels of beta-amyloid peptide and phosphorylated tau protein. To date, a precise and rigorous evaluation of PREGS blood concentrations during aging is lacking and the relationship between these concentrations and the memory loss associated with AD has not been established.

Primary objective To show that plasma concentrations of PREGS are decreased in AD patients (" case ") compared to free-AD subjects (" controls "), matched for gender and age.

Secondary objectives

• To show that plasma concentrations of PREGS are inversely correlated with the severity of memory deficits in AD patients.

• To show that plasma concentrations of PREGS are correlated with the memory scores in the controls.

• To show that plasma concentrations of PREGS decrease in the controls.

• To search for a relationship between some of PREGS metabolites and age or the severity of memory deficits.

This is a case-control study that will comprise 200 subjects aged over 70 years, including 100 outpatients with mild to moderate AD and 100 AD-free volunteer controls matched on age and gender. These two groups will be stratified into age-sub-groups [70-74] [75-79] [80-84] [85-89] > 90 years and will include 10 men and 10 women per sub-group.

AD patients and controls will be enrolled and evaluated in the geriatric centres of 5 hospitals namely BICETRE, BROCA, PAUL BROUSSE, PITIE-SALPETRIERE and ROTHSCHILD. They will all be submitted to a clinical examination, biological analyses, cognitive tests and a brain magnetic resonance imaging scan. Blood will be collected from all subjects for steroid analysis by gas chromatography-mass spectrometry, a sensitive and accurate methodology that allows simultaneous quantification of several steroids in the same individual sample. PREGS and some of its metabolites will be identified and quantified at the "Institute medical of heath" (INSERM U788).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 70 Years and older

Eligibility

Inclusion Criteria:

• Subjects aged over 70 years who have signed informed consent for participation to the study and are affiliated to a social security regimen.

• For patients: subjects with probable AD according to the DSM-IV criteria and the NINCDS/ADRDA criteria and with mild to moderate probable AD: MMSE score> 15.

• For Controls: subjects without cognitive deficits on neuropsychological tests: scores of MMSE > 26 and of the 5 Word test equal to 10/10 and of the Clock Drawing test equal to 7/7.

Exclusion Criteria:

• Guardianship

• History of cerebrovascular disease, Parkinson's disease, other known dementia, epilepsy

• Major depression

• Serious sensory disorders; deficits in language & comprehension

• Serious heart or hepatic insufficiencies, renal or respiratory failures

• Unstable diabetes or endocrine disorders, thyroid dysfunction, cancer, inflammatory syndrome, malnutrition

• Cognitive training during the 6 previous months

• Medications: steroids (HRT, androgens, corticoids), anti-depressants, cholinesterase inhibitors, thyroid hormones, synthetic anti-thyroids

• Contraindications for MRI: metallic implants & claustrophobia

Study Design

Observational Model: Case Control, Time Perspective: Prospective

Related Conditions & MeSH terms

• Alzheimer Disease

Locations

Country	Name	City	State
France	Assistance publique - Hôpitaux de Paris Hôpital Bicêtre	Le Kremlin Bicêtre
France	Inserm Umr 788	Le Kremlin Bicêtre
France	AP-HP Hôpital Rothschild	Paris
France	Assistance Publique - Hôpitaux de Paris Hôpital Broca	Paris
France	Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpétrière	Paris
France	Assistance Publique - Hôpitaux de Paris, Hôpital Paul Brousse	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentrations of PREGS determined by GC-MS		At the day of diagnostic blood collection	No
Secondary	Memory scores of the RL-RI test according to the GROBER and BUSCKE test		At the day of blood collection	No
Secondary	Plasma concentrations of PREGS metabolites		At the day of blood collection	No