Intravenous Immunoglobulin for Unverricht-Lundborg Disease.

Intravenous Immunoglobulin for Unverricht-Lundborg Disease: Single-patient Trial.

Single patient randomized double blind trial to assess whether intravenous immunoglobulin can improve the clinical outcome of a case suffering from Unverricht-Lundborg disease.

Study Overview

• Status: Unknown
• Conditions: Unverricht-Lundborg Disease
• Intervention / Treatment: Drug: Intravenous immunoglobulin

Detailed Description

Single patient randomized double blind trial to assess whether intravenous immunoglobulin can improve the clinical outcome of a case suffering from Unverricht-Lundborg disease (clinical and genetic diagnosis).

The patient was randomized to be treated with intravenous immunoglobulin or placebo 1:1 (crossover) once a month for at least one year.

Main objective: improvement of the action myoclonus. Secondary objectives: Improvement in the overall score and in individual sections of the Unified Myoclonus Rating Scale at one year; patient preferences based on results at the end of the trial.

The first analyst was scheduled at one year from the start of the trial. The program was to discuss the patient's analysis data and to let the patient decide in three possible ways: to continue the trial, to continue treatment with immunoglobulins, to suspend the treatment. Depending on the decision, it was planned to follow the patient throughout the year after the analysis, at least for one year.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 23 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Malattia di Unverricht-Lundborg (genetic diagnosis)

Exclusion Criteria:

• Contraindications to intravenous immunoglobulin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immunoglobulin; Intravenous immunoglobulin 25 grams (five 100 ml bottles, 5g/100ml), in 3 hours, once a month for one year.	Drug: Intravenous immunoglobulin; Intravenous drip.; Other Names: Venital
Placebo Comparator: Saline solution; Intravenous saline solution 500 ml (five 100 ml bottles), in 3 hours, once a month for one year.	Drug: Intravenous immunoglobulin; Intravenous drip.; Other Names: Venital

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of at least 20% of the action myoclonus at one year, measured with section 4 (Action Myoclonus) of the Unified Myoclonus Rating Scale.	The range for Action Myoclonus Score is 0 (best) - 160 (worst, , i.e. more severe involuntary movements). Percent change = 100 X (Placebo UMRS4 - Treatment UMRS4) / Placebo UMRS4).	monthly for one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unified Myoclonus Rating Scale (UMRS) overall score improvement.	The total value of the UMRS (range from 0 - best - to 365 - worst) is composed of the sum of 6 sections: (1) Patient Questionnaire (range 0-48), (2) Myoclonus at rest (range 0-108), (3) Stimulus Sensitivity (range 0-17), (4) Myoclonus with Action (range 0-160), (5) Functional Tests (0-28), (6) Global Disability Score (range 0-4).	monthly for one year
Patient's preference	The program was to discuss the patient's analysis data with the patient himself and to let him decide in three possible ways: (1) to continue the trial, (2) to continue treatment with immunoglobulins, (3) to suspend the treatment.The choice number 2 is considered a favorable outcome.	one year

Collaborators and Investigators

• Sponsor: Azienda Socio Sanitaria Territoriale di Mantova

Publications and helpful links

General Publications

• Lillie EO, Patay B, Diamant J, Issell B, Topol EJ, Schork NJ. The n-of-1 clinical trial: the ultimate strategy for individualizing medicine? Per Med. 2011 Mar;8(2):161-173. doi: 10.2217/pme.11.7.
• Guatelli JC, Gingeras TR, Richman DD. Alternative splice acceptor utilization during human immunodeficiency virus type 1 infection of cultured cells. J Virol. 1990 Sep;64(9):4093-8. doi: 10.1128/JVI.64.9.4093-4098.1990.

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2015
• Primary Completion (Actual): December 6, 2016
• Study Completion (Anticipated): December 30, 2017

Study Registration Dates

• First Submitted: October 27, 2017
• First Submitted That Met QC Criteria: November 21, 2017
• First Posted (Actual): November 24, 2017

Study Record Updates

• Last Update Posted (Actual): November 27, 2017
• Last Update Submitted That Met QC Criteria: November 22, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Unverricht-Lundborg disease; progressive myoclonus epilepsy; pharmacoresistant epilepsy
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Genetic Diseases, Inborn; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Epilepsy; Myoclonic Epilepsies, Progressive; Epilepsies, Myoclonic; Unverricht-Lundborg Syndrome; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous; gamma-Globulins; Rho(D) Immune Globulin
• Other Study ID Numbers: 200200; 2017-002147-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: We planned to publish the results of this single patient trial.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No