Condition category
Nervous System Diseases
Date applied
02/05/2017
Date assigned
24/05/2017
Last edited
24/05/2017
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims:
Alzheimer’s disease (AD) is the most common cause of dementia, affecting around 30 million individuals worldwide. It is caused by the abnormal build-up of various proteins in the brain to form what are known as amyloid plaques. The plaques are toxic to brain cells, and eventually cause their death, leading to the gradual decline in day-to-day memory and other mental functions. Serum amyloid P component (SAP) is a normal protein that occurs in everyone. It is produced in the liver and travels via the blood stream to reach other organs including the brain. Although only very small amounts of SAP enter the brain, it binds to the abnormal proteins in the brains of patients with AD. It forms part of the amyloid plaques and prevents them from breaking down. Therefore, preventing SAP from binding amyloid plaques may lead to faster breakdown of the amyloid plaques and so delay the progression of Alzheimer’s disease. There is also evidence that SAP directly damages brain cells and may contribute to the development of Alzheimer’s disease. Removal of SAP may reduce this damage to brain cells. A new drug has been developed, called CPHPC, which eliminates SAP almost completely from the blood and thereby stops SAP from reaching the brain. CPHPC may also remove the SAP already present in the brain. This may reduce the brain damage caused by the disease. The aim of this study is to explore the safety, tolerability and potential effectiveness of CPHPC in patients with mild AD.

Who can participate?
Patients aged 50-80 who have been diagnosed with mild AD.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive three injections per day of CPHPC into their tummy for 12 months. Those in the second group receive three injections per day of a placebo (dummy drug) into their tummy for 12 months. At the start of the study, over the 12 months of treatment, and one month later, participants in both groups undergo brain scanning to look at the effects of the treatment, as well as having blood and cerebrospinal fluid (the fluid found in the brain and spinal cord) samples taken for testing and completing assessments of their memory.

What are the possible benefits and risks of participating?
It is not known whether taking part in this study will benefit participants however those who receive the CPHPC may benefit from a reduced amount of SAP in the blood and removal of SAP from the brain throughout the period of treatment. There are no anticipated risks, however as this is a study looking at a new experimental drug there is a potential that patients may experience side effects.

Where is the study run from?
National Institute for Health Research (UK)

When is study starting and how long is it expected to run for?
August 2015 to August 2020

Who is funding the study?
Education Endowment Foundation (UK)

Who is the main contact?
Mr Chinaza Ezirim
c.ezirim@ucl.ac.uk

Trial website

Contact information

Type

Public

Primary contact

Mr Chinaza Ezirim

ORCID ID

Contact details

Comprehensive Clinical Trials Unit
University College London
4 Stephenson Way
London
NW1 2HE
United Kingdom
+44 20 3549 5438
c.ezirim@ucl.ac.uk

Additional identifiers

EudraCT number

2016-003284-19

ClinicalTrials.gov number

Protocol/serial number

33953

Study information

Scientific title

DESPIAD: A double-blind placebo controlled randomised phase IIb trial of SAP depletion by CPHPC in mild Alzheimer’s disease

Acronym

DESPIAD

Study hypothesis

The aim of this study is to determine whether Serum Amyloid P component (SAP) reduction improves established clinical and other measures of Alzheimer’s disease.

Ethics approval

South Central – Berkshire B REC, 24/01/2017, ref: 16/SC/0590

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

See additional files

Condition

Specialty: Dementias and neurodegeneration, Primary sub-specialty: Dementia; UKCRC code/ Disease: Neurological/ Demyelinating diseases of the central nervous system

Intervention

Participants will be randomly allocated 1:1 into 2 groups by minimisation/

Intervention group: Participants receive (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl] pyrrolidine-2-carboxylic acid, (CPHPC) 60 mg (0.3 ml) t.d.s by subcutaneous (s.c.) injection three times daily for 12 months

Control group: Participants receive a placebo (0.3 ml t.d.s of water for injection adjusted to pH 5.0 with sodium hydroxide or hydrochloric acid by s.c. injection, with no active component or other additives, three times daily for 12 months

Participants are followed up at month 13 which involves a review of adverse events and concomitant medications, general physical and neurological examination, vital signs, ECG, bloods, urine tests and cognitive testing.

Intervention type

Other

Phase

Phase II

Drug names

Primary outcome measures

Safety and tolerability of CPHPC is assessed by MRI at baseline, 3 months and 12 months.

Secondary outcome measures

1. Rates of whole brain and hippocampal atrophy is assessed using quantitative semi-automated analysis of volumetric MRI of brain scans obtained at baseline and 12 months
2. Cognition is assessed using a version of the Preclinical Alzheimer Cognitive Composite (PACC), comprising: Face Name Associative Memory Performance, Wechsler Logical Memory (paragraph recall), Mini Mental State Examination (MMSE) and Digit Symbol Substitution Test score from the Wechsler Adult Intelligence Scale–Revised; verbal fluency; an in-house computer-based reaction time task; Clinical Dementia Rating (CDR), and Neuropsychiatric Inventory (NPI). The tests will be performed at baseline, 6, 12, and 13 months.
3. Other qualitative and quantitative MRI parameters which provide high-resolution maps of grey and white matter microstructure, and so can serve as a biomarker of disease modification by CPHPC are assessed by CSF fluid at baseline and 12 months
4. Amyloid PET-CT is assessed using florbetapir (18F) PET-CT by single intravenous dose and scanning at the Institute of Nuclear Medicine, UCLH at baseline (or within the previous 4 weeks), and 12 months.
5. Lumbar puncture is assessed by measuring CSF concentrations of SAP, CPHPC, Aβ1-42, total and phosphorylated τ at baseline and 12 months
6. Plasma SAP concentration is assessed by blood test at baseline, 3, 6, 9, 12 and 13 months

Overall trial start date

25/08/2015

Overall trial end date

01/08/2020

Reason abandoned

Eligibility

Participant inclusion criteria

1. A clinical diagnosis of mild AD (MMSE 20-28 inclusive)
2. Male or female between 50-80 years of age inclusive
3. Supportive evidence of AD pathology from:
3.1. MRI brain scan consistent with a diagnosis of AD
3.2. Florbetapir (18F) PET imaging consistent with a diagnosis of AD
4. Participant must live with a partner, relative or carer who can both attend study visits and oversee the management of the dosing of medication by s.c. injection
5. Agree to undergo MRI, PET imaging and lumbar puncture
6. Ability to provide written informed consent
7. Women of child bearing potential3 and males willing to use effective4 contraception for the duration and 30 days post completion of trial treatment
8. In the opinion of the CI or delegate, adequate understanding of written and verbal information in English

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 100; UK Sample Size: 100

Participant exclusion criteria

1. Ongoing clinically significant depression, in the opinion of the PI likely to impede completion of the trial, or other diseases or drugs influencing cognition; anti-depressant medication stable for more than 3 months is acceptable
2. Significantly abnormal renal (eGFR <50mls/min/m2) or hepatic enzyme (alanine aminotransferase) values two fold or greater above the upper limit of the reference range
3. Current use of warfarin, rivaroxaban, apixaban and or dabigatran; low dose aspirin or clopidogrel are permitted
4. Current use of cholinesterase inhibitors or memantine unless maintained on a stable dose for at least 3 months prior to randomisation
5. Use of other experimental drugs within 3 months of randomisation
6. Pregnancy or lactation* (current, or planned in the next 13 months)
7. Any medical condition that could be expected to progress, recur, or change to an extent that it could bias the assessment of the clinical or mental status of the participant to a significant degree or put the participant at special risk in the opinion of the investigator
8. Any known hypersensitivity to the constituents or the vehicle of CPHPC
9. Any known claustrophobia
10. Weight greater than 150 Kg

*The safety of CPHPC in pregnancy is unknown. Teratogenicity risks for female partners of males being treated with CPHPC are unknown.

Recruitment start date

01/08/2017

Recruitment end date

01/08/2018

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Leonard Wolfson Experimental Neurology Centre
National Hospital for Neurology & Neurosurgery Queen Square
London
WC1N 3BG
United Kingdom

Sponsor information

Organisation

University College London

Sponsor details

Comprehensive Clinical Trials Unit
Gower Street
London
WC1E 6BT
United Kingdom
+44 203 549 5438
c.ezirim@ucl.ac.uk

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer reviewed and open access journals.

IPD Sharing statement:
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/08/2021

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes