Long-Term Study of Nitisinone to Treat Alkaptonuria

This study has been completed.

Study NCT00107783 Information provided by National Institutes of Health Clinical Center (CC)

First Received on April 7, 2005. Last Updated on December 20, 2010 History of Changes

Results First Received: December 20, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Single Blind (Outcomes Assessor); Primary Purpose: Treatment
Condition:	Alkaptonuria
Intervention:	Drug: Nitisinone (NTBC)

Participant Flow

Hide Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Patients were enrolled at the NIH Clinical Center between April 2005 and March 2006.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
Control	No treatment
Nitisinone-treated	Subjects received nitisinone 2 mg orally, once daily.

Participant Flow: Overall Study

	Control	Nitisinone-treated
STARTED	20	20
COMPLETED	17	16
NOT COMPLETED	3	4
Adverse Event	0	2
Death	0	1
Withdrawal by Subject	2	0
Second hip replacement	1	1

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Control	No treatment
Nitisinone-treated	Subjects received nitisinone 2 mg orally, once daily.

Baseline Measures

	Control	Nitisinone-treated	Total
Number of Participants [units: participants]	20	20	40
Age [units: participants]
<=18 years	0	0	0
Between 18 and 65 years	20	19	39
>=65 years	0	1	1
Age [units: years] Mean ± Standard Deviation	51.3 ± 6.5	52.2 ± 7.9	51.7 ± 7.1
Gender [units: participants]
Female	5	8	13
Male	15	12	27
Region of Enrollment [units: participants]
United States	20	20	40
Total Range of Motion (ROM) Worse Hip ^[1] [units: degrees] Mean ± Standard Deviation	46.4 ± 16.1	39.0 ± 12.7	42.7 ± 14.8
Schober's test ^[2] [units: cm] Mean ± Standard Deviation	11.42 ± 1.04	10.86 ± 0.73	11.14 ± 0.93
Functional Reach Assessment ^[3] [units: cm] Mean ± Standard Deviation	10.22 ± 2.92	8.98 ± 3.10	9.60 ± 3.04
Timed get up and go ^[4] [units: seconds] Mean ± Standard Deviation	7.56 ± 1.40	9.70 ± 4.10	8.63 ± 3.21
6 minute walk test ^[5] [units: ft] Mean ± Standard Deviation	1578 ± 205	1336 ± 369	1457 ± 319

[1]	The total (internal + external) range of motion (ROM) of the worse hip.
[2]	Schober's test measures a patient's ability to flex his/her lower back. The examiner makes a mark at L5 (fifth lumbar vertebra) and places one finger 5 cm below and another finger 10 cm above this mark. The patient is asked to touch his/her toes. The examiner measures the increase in distance between the two fingers.
[3]	Functional reach assessment measures the difference between the length of a person's outstretched arm and their maximal reach forward, while maintaining balance.
[4]	In timed get up and go, the patient is asked to stand up from a standard chair and walk a distance of 3 meters, turn around and walk back to the chair and sit down. The examiner measures the time it takes for the patient to perform this series of tasks.
[5]	The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.

Outcome Measures

Show All Outcome Measures

1. Primary:

Change in Total ROM Worse Hip. [ Time Frame: Measured at baseline and at 36 months ]

Show Outcome Measure 1

2. Secondary:

Change in Schober's Test [ Time Frame: Measured at baseline and at 36 months ]

Show Outcome Measure 2

3. Secondary:

Change in Functional Reach Assessment [ Time Frame: Measured at baseline and at 36 months ]

Show Outcome Measure 3

4. Secondary:

Change in Timed Get up and go [ Time Frame: Measured at baseline and at 36 months ]

Show Outcome Measure 4

5. Secondary:

Change in 6 Minute Walk Test (6MWT) [ Time Frame: Measured at baseline and at 36 months ]

Show Outcome Measure 5

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

All Principal Investigators ARE employed by the organization sponsoring the study.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Small number of patients involved in study and several patients dropped out; primary outcome parameter selection possibly inappropriate because hip joint damage that is already present may be irreversible.

Results Point of Contact:

Name/Title: William Gahl, MD/Clinical Director
Organization: NHGRI
phone: 301-402-2739
e-mail: gahlw@mail.nih.gov

Publications:

Introne WJ, Phornphutkul C, Bernardini I, McLaughlin K, Fitzpatrick D, Gahl WA. Exacerbation of the ochronosis of alkaptonuria due to renal insufficiency and improvement after renal transplantation. Mol Genet Metab. 2002 Sep-Oct;77(1-2):136-42.

Phornphutkul C, Introne WJ, Perry MB, Bernardini I, Murphey MD, Fitzpatrick DL, Anderson PD, Huizing M, Anikster Y, Gerber LH, Gahl WA. Natural history of alkaptonuria. N Engl J Med. 2002 Dec 26;347(26):2111-21.

Janocha S, Wolz W, Srsen S, Srsnova K, Montagutelli X, Guenet JL, Grimm T, Kress W, Muller CR. The human gene for alkaptonuria (AKU) maps to chromosome 3q. Genomics. 1994 Jan 1;19(1):5-8.

Responsible Party:	William A. Gahl, M.D./National Human Genome Research Institute, National Institutes of Health
ClinicalTrials.gov Identifier:	NCT00107783 History of Changes
Other Study ID Numbers:	050076, 05-HG-0076
Study First Received:	April 7, 2005
Results First Received:	December 20, 2010
Last Updated:	December 20, 2010
Health Authority:	United States: Federal Government