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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Completed

CT.gov ID

NCT00912886

Collaborator

(none)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease

Detailed 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).

Study Design

Study Type:

Observational

Actual Enrollment :

90 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

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

Study Start Date :

Sep 1, 2009

Actual Primary Completion Date :

Sep 1, 2011

Actual Study Completion Date :

Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
1: Case Patients with early and moderate AD
2: Controls AD free volunteer-controls matched for gender and age

Outcome Measures

Primary Outcome Measures

Plasma concentrations of PREGS determined by GC-MS [At the day of diagnostic blood collection]

Secondary Outcome Measures

Memory scores of the RL-RI test according to the GROBER and BUSCKE test [At the day of blood collection]
Plasma concentrations of PREGS metabolites [At the day of blood collection]

Eligibility Criteria

Criteria

Ages Eligible for Study:

70 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Assistance publique - Hôpitaux de Paris Hôpital Bicêtre	Le Kremlin Bicêtre	France	94275
2	Inserm Umr 788	Le Kremlin Bicêtre	France	94276
3	AP-HP Hôpital Rothschild	Paris	France	75012
4	Assistance Publique - Hôpitaux de Paris Hôpital Broca	Paris	France	75013
5	Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpétrière	Paris	France	75013
6	Assistance Publique - Hôpitaux de Paris, Hôpital Paul Brousse	Villejuif	France	94800

Sponsors and Collaborators

Assistance Publique - Hôpitaux de Paris

Investigators

Principal Investigator: Sebastien Weill-Engerer, MD, Assistance Publique - Hôpitaux de Paris Hôpital Rothschild
Study Director: Yvette Akwa, PhD, INSERM U788