+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial



Intravenous immunoglobulin for treatment of mild-to-moderate Alzheimer's disease: a phase 2, randomised, double-blind, placebo-controlled, dose-finding trial



Lancet. Neurology 12(3): 233-243



Three small trials suggest that intravenous immunoglobulin can affect biomarkers and symptoms of mild-to-moderate Alzheimer's disease. We tested the safety, effective dose, and infusion interval of intravenous immunoglobulin in such patients. We did a multicentre, placebo-controlled phase 2 trial at seven sites in the USA and five in Germany. Participants with probable Alzheimer's disease aged 50-85 years were randomly assigned (by a computer-generated randomisation sequence, with block sizes of eight) to infusions every 4 weeks (0·2, 0·5, or 0·8 g intravenous immunoglobulin per kg bodyweight, or placebo) or infusions every 2 weeks (0·1, 0·25, or 0·4 g/kg, or placebo). Patients, caregivers, investigators assessing outcomes, and staff at imaging facilities and the clinical research organisation were masked to treatment allocation, but dispensing pharmacists, the statistician, and the person responsible for final PET analyses were not. Treatment was masked with opaque pouches and infusion lines. The primary endpoint was median area under the curve (AUC) of plasma amyloid β (Aβ)(1-40) between the last infusion and the final visit (2 weeks or 4 weeks depending on infusion interval) in the intention-to-treat population. The trial is registered at ClinicalTrials.gov (NCT00812565) and controlled-trials.com (ISRCTN64846759). 89 patients were assessed for eligibility, of whom 58 were enrolled and 55 included in the primary analysis. Median AUC of plasma Aβ(1-40) was not significantly different for intravenous immunoglobulin compared with placebo for five of the six intervention groups (-18·0 [range -1347·0 to 1068·5] for 0·2 g/kg, -364·3 [-5834·5 to 1953·5] for 0·5 g/kg, and -351·8 [-1084·0 to 936·5] for 0·8 g/kg every 4 weeks vs -116·3 [-1379·0 to 5266·0] for placebo; and -13·8 [-1729·0 to 307·0] for 0·1 g/kg, and -32·5 [-1102·5 to 451·5] for 0·25 g/kg every 2 weeks vs 159·5 [51·5 to 303·0] for placebo; p>0·05 for all). The difference in median AUC of plasma Aβ(1-40) between the 0·4 g/kg every 2 weeks group (47·0 [range -341·0 to 72·5]) and the placebo group was significant (p=0·0216). 25 of 42 (60%) patients in the intervention group versus nine of 14 (64%) receiving placebo had an adverse event. Four of 42 (10%) patients in the intravenous immunoglobulin group versus four of 14 (29%) receiving placebo had a serious adverse event, including one stroke in the intervention group. Intravenous immunoglobulin may have an acceptable safety profile. Our results did not accord with those from previous studies. Longer trials with greater power are needed to assess the cognitive and functional effects of intravenous immunoglobulin in patients with Alzheimer's disease.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 036748722

Download citation: RISBibTeXText

PMID: 23375965

DOI: 10.1016/s1474-4422(13)70014-0


Related references

A randomized, double-blind, placebo-controlled dose-finding trial of intravenous immunoglobulin (IVIG; Octagam 10%, Octapharma AG) in patients with mild to moderate Alzheimer's disease (GAM10-04). Alzheimer's & Dementia 7(4): E55-E56, 2011

Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: A double blind, randomised, placebo controlled trial. Journal of Neurology Neurosurgery & Psychiatry 74(7): 863-866, 2003

Safety and pharmacology of a single intravenous dose of ponezumab in subjects with mild-to-moderate Alzheimer disease: a phase I, randomized, placebo-controlled, double-blind, dose-escalation study. Clinical Neuropharmacology 36(1): 14-23, 2013

Memantine treatment in patients with mild to moderate Alzheimer's disease: results of a randomised, double-blind, placebo-controlled 6-month study. Journal of Alzheimer's Disease 11(4): 471-479, 2007

A confirmatory phase 3 randomized, double-blind, placebo-controlled study of the safety and effectiveness of immune globulin intravenous (Human), 10% solution (GAMMAGARD LIQUID/KIOVIG) for the treatment of mild to moderate Alzheimer's disease:. Alzheimer's & Dementia 7(4): S783-S784, 2011

Safety and pharmacokinetics of PF-04360365 following a single-dose intravenous infusion in Japanese subjects with mild-to-moderate Alzheimer's disease: a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study. International Journal of Clinical Pharmacology and Therapeutics 51(12): 911-923, 2013

Safety and efficacy of idalopirdine, a 5-HT6 receptor antagonist, in patients with moderate Alzheimer's disease (LADDER): a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. Neurology 13(11): 1092-1099, 2014

A randomized, double-blind, placebo-controlled trial of modafinil for the treatment of apathy in individuals with mild-to-moderate Alzheimer's disease. Journal of Clinical Psychiatry 73(6): 796-801, 2012

Efficacy and safety of tau-aggregation inhibitor therapy in patients with mild or moderate Alzheimer's disease: a randomised, controlled, double-blind, parallel-arm, phase 3 trial. Lancet 388(10062): 2873-2884, 2016

Co-crystal of Tramadol-Celecoxib in Patients with Moderate to Severe Acute Post-surgical Oral Pain: A Dose-Finding, Randomised, Double-Blind, Placebo- and Active-Controlled, Multicentre, Phase II Trial. Drugs in R&d 18(2): 137-148, 2018

Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomized and placebo-controlled trial. Journal of Clinical Pharmacy and Therapeutics 28(1): 53-59, 2003

Memantine treatment in patients with mild to moderate Alzheimer's disease already receiving a cholinesterase inhibitor: a randomized, double-blind, placebo-controlled trial. Current Alzheimer Research 5(1): 83-89, 2008

Clinical efficacy and safety of huperzine Alpha in treatment of mild to moderate Alzheimer disease, a placebo-controlled, double-blind, randomized trial. Zhonghua Yi Xue Za Zhi 82(14): 941-944, 2002

Benralizumab for patients with mild to moderate, persistent asthma (BISE): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. Respiratory Medicine 5(7): 568-576, 2017

Clinical trial on Neurapas versus placebo in patients with mild to moderate depressive symptoms: a placebo-controlled, randomised double-blind study Phase IV: Clinical trial. Complementary Therapies in Medicine 2(1): 5-13, 1994