Ciclosporin in HTLV-1 Associated Myelopathy/ Tropical Spastic Paraparesis (HAM/TSP)

NCT00773292 | Completed Phase 2 Results DMC

• 1 other identifier: Cro423
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

HAM/TSP is a chronic disease of the spinal cord, caused by a virus called HTLV-I. Worldwide approximately 20 million persons are infected.Infection with HTLV-I is lifelong, and about 3% of infected persons will develop this chronic debilitating disease, of which half will become wheelchair dependent. We, and others, have shown a strong and persistent immune response to HTLV-I in carriers and patients with HAM/TSP, but this fails to clear the virus. However, carriers with a low burden of virus in the blood have a low risk of developing disease. The immune response in these carriers seems better able to kill infected cells. A less efficient response is associated with a higher viral burden that drives the immune response with a resultant release of chemicals by the immune cells that inadvertently cause harm, most especially to cells in the spinal cord. Our understanding of HAM/TSP suggests that targeting the immune response should improve the health of our patients especially if the disease is diagnosed early. To identify the best type of treatment we are planning a series of studies of drugs that target the immune response in different ways. Each has been used in other inflammatory conditions but never before studied in HAM/TSP. We aim to study the extent and duration of the clinical response and to associate this with the different effects that the therapies have on the immune response and on the number of HTLV-I infected cells in the blood. This in turn will improve our knowledge and understanding of the disease and should lead to better therapy. This application is in relation to the first study - to explore that therapeutic benefit of ciclosporin in patients with HAM/TSP.

Conditions

HTLV I Associated Myelopathy

Keywords

HAM/TSP

Outcome Measures

Primary Outcomes (1)

• Number of Patient With Lack of Objective Clinical Improvement

  Lack of objective clinical improvement after three months of therapy. Objective improvement was defined as any of the following comparing baseline measurements to 12, 24 and 48 weeks: i) one point decrease in the IPEC 1 scale (Instituto de Pesquisa Clínica Evandro Chagas), ii) \>30% improvement in 10 m timed walk, iii) visual analogue pain score reduced by \>2 points, iv) reduction of frequency or nocturia by greater than one or reduction of residual volume by more than 10% at two consecutive visits. Proof of concept study and therefore outcomes report is descriptive only. No statistical test appropriate.

  up to 12 months

Secondary Outcomes (1)

• Change in Timed Walk Rank Between Baseline and 12 Weeks

  0, 12 weeks

Study Arms (1)

ciclosporin

EXPERIMENTAL

48 weeks treatment with ciclosporin

Drug: ciclosporin

Interventions

ciclosporin DRUG

Ciclosporin 2.5 - 5mg/kg/day in two equally divided doses. dose adjusted according to trough ciclosporin concentration

ciclosporin

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Early (less than 2 years) HAM
• Progressing (within past 3 months) HAM
• Important to study the effect of therapy on disease that is most active as most likely to detect and measure improvement

You may not qualify if:

• HIV infection
• Tuberculosis, strongyloidiasis or other infection related to immune compromise
• Hepatitis B \& C viral infections
• Malignancy

Sponsors & Collaborators

• Imperial College London: lead
• Medical Research Council: collaborator
• University Hospital Birmingham: collaborator
• Imperial College Healthcare NHS Trust: collaborator

Study Sites (1)

National Centre for Human Retrovirology

London, W2 1NY, United Kingdom

Location

Related Publications (1)

• Martin F, Castro H, Gabriel C, Adonis A, Fedina A, Harrison L, Brodnicki L, Demontis MA, Babiker AG, Weber JN, Bangham CR, Taylor GP. Ciclosporin A proof of concept study in patients with active, progressive HTLV-1 associated myelopathy/tropical spastic paraparesis. PLoS Negl Trop Dis. 2012;6(6):e1675. doi: 10.1371/journal.pntd.0001675. Epub 2012 Jun 12.

  PMID: 22720101 RESULT

MeSH Terms

Conditions

Paraparesis, Tropical Spastic

Interventions

Cyclosporine

Condition Hierarchy (Ancestors)

Myelitis; Central Nervous System Infections; Infections; HTLV-I Infections; Deltaretrovirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Graham P Taylor
• Organization: Imperial College London

g.p.taylor@imperial.ac.uk

0207 594 3910

Study Officials

• Graham P Taylor

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2008
• First Posted: October 16, 2008
• Study Start: August 1, 2006
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: September 9, 2021
• Results First Posted: September 9, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)