Pilot-Study of Thalidomide in Amyotrophic Lateral Sclerosis (ALS)

Charité University Medicine Berlin

Status and phase

Terminated

Phase 2

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Treatments

Drug: Thalidomide (drug)

Study type

Interventional

Funder types

Other

Identifiers

NCT00231140

THL-ALS01

Details and patient eligibility

About

Neuroinflammation has recently emerged as a significant contributor to motor neuron damage. ALS tissue is characterized by inflammatory changes that are observed in both sporadic and familial ALS and in the ALS superoxide dismutase 1 (SOD1) transgenic mouse model. They include an accumulation of large numbers of activated microglia and astrocytes.

Proinflammatory cytokines, such as tumor necrosis factor (TNF-), are robustly upregulated in ALS. The receptor for tumor necrosis factor- (TNF-R1) is elevated at late presymptomatic as well as symptomatic phases of disease. TNF acts as a principal driver for neuroinflammation in ALS, while several co-stimulating cytokines and chemokines act to potentiate the TNF effects [4-6].

We propose an investigational therapy of ALS with oral administration of thalidomide. The rationale for this study is based on the anti-inflammatory properties of thalidomide through the modulation of inflammatory cytokines such as TNF. The primary aim of the trial is to determine whether treatment with thalidomide is safe and well tolerated in conjunction with riluzole and whether patients with ALS can tolerate daily doses of up to 400 mg. The trial is designed as feasibility study in planning for a larger phase IIb/III trial of efficacy.

Full description

Study drug will be provided as 50 mg tablets. Patients will be instructed to take 2 tablets orally once a day during the evening at least 60 minutes after a meal. Thalidomide will be administered starting at 100 mg (Group 1) for 6 weeks. Thereafter, the dose will be increased every week by 50mg until reaching the dose of 400 mg/day. This treatment is continued for 12 weeks. Thalidomide is administered in conjunction with the standard treatment of riluzole (100mg/day).

Sex

All

Ages

25 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

patients aged 25 and 80 years
female patients who are either postmenopausal for at least 24 month or who are willing and able to practice the methods of contraception following the Pharmion-Risk Managment Program (PRMP)
Male patients who are willing and able to practice the methods of contraception along with their female partners of childbearing potential following the PRMP
Clinical diagnosis of probable and definite ALS
Sporadic or familial ALS
Onset of pareses for no more than 4 years
Vital capacity equal to or more than 65% of the predicted value
Treatment with riluzole 100mg/day
Patients who are willing to give informed consent

Exclusion criteria

pregnancy or breast feeding
female patients who are unwilling or unable to practice the methods of contraception following the Pharmion-Risk Managment Program (PRMP)
Male patients who are willing and able to practice the methods of contraception along with their female partners of childbearing potential following the PRMP
Patients unlikely to comply with the PRMP and other study requirements
Patients with significant sensory abnormalities, dementia, uncompensated medical illnesses and psychiatric disorders
Laboratory abnormalities consistent with clinically significant cardiovascular, respiratory, haematological, metabolic, hepatic and renal disease
Infectious disease including HIV, hepatitis B and C
monoclonal gammopathy of unknown significance (MGUS)
History of substance abuse within the past year
History of recurrent thrombosis
Continuous non-invasive ventilation (ventilation-free interval equal to or less than 2 hours daily)
Tracheotomy and invasive ventilation
Treatment with investigational drug within 3 months prior to screening
patients with clinically signifikant sensory polyneuropathy (inflammatory neuropathy cause and treatment sensory sum score - ISS ≥ 2)
patients with sleep disorder (Epworth Sleeping Scale-ESS ≥ 10)