Choline Alphoscerate-Nimodipine in Vascular Cognitive Impairment

NCT03228498 | Completed Phase 2

• 1 other identifier: 2015-003188-13
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess whether the combination of choline alphoscerate 1200mg per day and nimodipine 90mg per day given orally is more effective than the combination nimodipine placebo in reducing cognitive decline in patients with subcortical vascular cognitive impairment

Conditions

Vascular Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Cognitive decline evaluated by the change of MoCA test score compared with Baseline

  Cognitive decline: expressed as the loss of at least 2 points on Montreal Cognitive Assessment (MoCA) test

  12 months

Secondary Outcomes (8)

• Evaluation of selective attention

  12 months

• Evaluation of divided attention

  12 months

• Evaluation of maintained attention

  12 months

• Evaluation of memory

  12 months

• Assessment of functional status

  12 months

Study Arms (2)

Choline alphoscerate

EXPERIMENTAL

Drug: Choline alphoscerate 1200 mg per day and Nimodipine 90 mg per day concomitant administration

Drug: Choline alphoscerate

Placebo

PLACEBO COMPARATOR

Placebo and Drug: Nimodipine 90 mg per day only concomitant administration

Drug: Placebo

Interventions

Choline alphoscerate DRUG

Choline alphoscerate 600 mg b.i.d plus Nimodipine 30 mg t.i.d

Also known as: Delecit

Choline alphoscerate

Placebo DRUG

Placebo b.i.d plus Nimodipine 30 mg t.i.d

Placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Cognitive impairment from mild to moderate degree defined by a Clinical Deterioration Rating (CDR) score range between 0.5 and 2.0.
• Evidence on brain MRI of white matter hyperintensities (leukoaraiosis of moderate or severe degree according to the modified Fazekas visual scale and/or presence of lacunar infarcts).
• Consent to participation in the study.

You may not qualify if:

• Absence of objectionable cognitive impairment or presence of dementia of severe degree defined by CDR score \> 2.0.
• Unavailability of brain MRI (in case of absolute contraindications, the use of cranial CT is allowed).
• Expected poor compliance with the study protocol.
• Past diagnosis of major depression, schizophrenia, major anxiety syndrome, or manic- depressive illness.
• Diagnosis of degenerative cognitive impairment based on clinical and/or neuroradiological findings (i.e., patients with prevailing memory impairment, or with medial temporal atrophy on brain MRI in absence of evident vascular abnormalities; i.e., Alzheimer disease as defined using the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria, Parkinson disease, Huntington disease, frontotemporal dementia).
• Diagnosis of cognitive impairment from other causes (i.e., vitamine B12 and folic acid deficiency, thyroid disorders, metabolic diseases, head trauma, tumor or infections of the central nervous system, normal pressure hydrocephalus).
• Medical conditions expected to progress, recur, or change to such a degree to interfere with the assessment of the clinical and mental status.
• Clinically relevant cardiac or pulmonary insufficiency.
• Relevant electrocardiograph abnormalities; bradycardia (50 bpm) or tachycardia (120 bpm) under resting conditions.
• Myocardial infarction within the past 6 months.
• Stroke still requiring neurological rehabilitation.
• Severe/untreated blood pressure (systolic 180 mm Hg, diastolic 95 mm Hg).
• Clinically relevant liver function impairment.
• Insulin-dependent diabetes mellitus.
• Idiopathic epilepsy and anti-epileptic treatment.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Careggi: lead
• MDM S.p.A.: collaborator

Study Sites (1)

Stroke Unit, VAS-COG clinic, Azienda Ospedaliero Universitaria Careggi

Florence, 50134, Italy

Location

Related Publications (13)

• O'Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, Bowler JV, Ballard C, DeCarli C, Gorelick PB, Rockwood K, Burns A, Gauthier S, DeKosky ST. Vascular cognitive impairment. Lancet Neurol. 2003 Feb;2(2):89-98. doi: 10.1016/s1474-4422(03)00305-3.

  PMID: 12849265 BACKGROUND

• Pantoni L. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges. Lancet Neurol. 2010 Jul;9(7):689-701. doi: 10.1016/S1474-4422(10)70104-6.

  PMID: 20610345 BACKGROUND

• Wardlaw JM, Smith C, Dichgans M. Mechanisms of sporadic cerebral small vessel disease: insights from neuroimaging. Lancet Neurol. 2013 May;12(5):483-97. doi: 10.1016/S1474-4422(13)70060-7.

  PMID: 23602162 BACKGROUND

• Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE, Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V, Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B, Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. Lancet Neurol. 2013 Aug;12(8):822-38. doi: 10.1016/S1474-4422(13)70124-8.

  PMID: 23867200 BACKGROUND

• Pantoni L. Treatment of vascular dementia: evidence from trials with non-cholinergic drugs. J Neurol Sci. 2004 Nov 15;226(1-2):67-70. doi: 10.1016/j.jns.2004.09.014.

  PMID: 15537523 BACKGROUND

• Smith EE, Cieslak A, Barber P, Chen J, Chen YW, Donnini I, Edwards JD, Frayne R, Field TS, Hegedus J, Hanganu V, Ismail Z, Kanji J, Nakajima M, Noor R, Peca S, Sahlas D, Sharma M, Sposato LA, Swartz RH, Zerna C, Black SE, Hachinski V. Therapeutic Strategies and Drug Development for Vascular Cognitive Impairment. J Am Heart Assoc. 2017 May 5;6(5):e005568. doi: 10.1161/JAHA.117.005568. No abstract available.

  PMID: 28476873 BACKGROUND

• Di Perri R, Coppola G, Ambrosio LA, Grasso A, Puca FM, Rizzo M. A multicentre trial to evaluate the efficacy and tolerability of alpha-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. J Int Med Res. 1991 Jul-Aug;19(4):330-41. doi: 10.1177/030006059101900406.

  PMID: 1916007 BACKGROUND

• Pantoni L, Carosi M, Amigoni S, Mascalchi M, Inzitari D. A preliminary open trial with nimodipine in patients with cognitive impairment and leukoaraiosis. Clin Neuropharmacol. 1996 Dec;19(6):497-506. doi: 10.1097/00002826-199619060-00003.

  PMID: 8937788 BACKGROUND

• Pantoni L, del Ser T, Soglian AG, Amigoni S, Spadari G, Binelli D, Inzitari D. Efficacy and safety of nimodipine in subcortical vascular dementia: a randomized placebo-controlled trial. Stroke. 2005 Mar;36(3):619-24. doi: 10.1161/01.STR.0000155686.73908.3e. Epub 2005 Feb 3.

  PMID: 15692125 BACKGROUND

• Nasreddine ZS, Phillips NA, Bedirian V, Charbonneau S, Whitehead V, Collin I, Cummings JL, Chertkow H. The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. 2005 Apr;53(4):695-9. doi: 10.1111/j.1532-5415.2005.53221.x.

  PMID: 15817019 BACKGROUND

• Poggesi A, Salvadori E, Pantoni L, Pracucci G, Cesari F, Chiti A, Ciolli L, Cosottini M, Del Bene A, De Stefano N, Diciotti S, Dotti MT, Ginestroni A, Giusti B, Gori AM, Nannucci S, Orlandi G, Pescini F, Valenti R, Abbate R, Federico A, Mascalchi M, Murri L, Inzitari D. Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers-The VMCI-Tuscany Study: Rationale, Design, and Methodology. Int J Alzheimers Dis. 2012;2012:608013. doi: 10.1155/2012/608013. Epub 2012 Apr 8.

  PMID: 22550606 BACKGROUND

• Salvadori E, Poggesi A, Donnini I, Rinnoci V, Chiti G, Squitieri M, Tudisco L, Fierini F, Melone A, Pescini F, Pantoni L. Efficacy and Safety of the Association of Nimodipine and Choline Alphoscerate in the Treatment of Cognitive Impairment in Patients with Cerebral Small Vessel Disease. The CONIVaD Trial. Drugs Aging. 2021 Jun;38(6):481-491. doi: 10.1007/s40266-021-00852-8. Epub 2021 Apr 15.

  PMID: 33855653 DERIVED

• Salvadori E, Poggesi A, Donnini I, Rinnoci V, Chiti G, Squitieri M, Tudisco L, Fierini F, Melone A, Pescini F, Pantoni L. Association of nimodipine and choline alphoscerate in the treatment of cognitive impairment in patients with cerebral small vessel disease: study protocol for a randomized placebo-controlled trial-the CONIVaD trial. Aging Clin Exp Res. 2020 Mar;32(3):449-457. doi: 10.1007/s40520-019-01229-z. Epub 2019 May 30.

  PMID: 31148099 DERIVED

MeSH Terms

Interventions

Glycerylphosphorylcholine

Intervention Hierarchy (Ancestors)

Glycerophosphates; Triose Sugar Alcohols; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Glycerophospholipids; Phosphatidic Acids; Phospholipids; Membrane Lipids; Lipids; Lecithins; Phosphatidylcholines

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double Blind (Participant, Investigator)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 19, 2017
• First Posted: July 25, 2017
• Study Start: May 2, 2017
• Primary Completion: July 9, 2019
• Study Completion: July 9, 2019
• Last Updated: January 13, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)