ErythrocytosisPhase 1/2CoCMSNCT01187108
Study of Cobalt's Role in Excessive Erythrocytosis Among High Altitude Dwellers in Cerro de Pasco, Peru
A Phase 1/2 study testing N-acetylcysteine and Acetazolamide in people with Erythrocytosis and Mountain Sickness, run by University of Colorado, Denver at 1 site in Peru.
Trial summary
Chronic mountain sickness is characterized by excessive red blood cell production which causes sludging of the vascular system. This high viscosity blood causes heart failure, cognitive dysfunction, and strokes. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Erythrocytosis, Mountain Sickness
- What is being tested?
- N-acetylcysteine and Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 85 participants
- Where
- 1 sitePeru
- Study dates
- Jun 2013to Sep 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males over 17 years of age
- Hematocrit > 70%
- Chronic Mountain Sickness score (CMS) > 6
- Able to give informed consent and follow instructions in written Spanish
Who cannot join
- CMS > 15
- Underlying lung disease, smoking, or oxygen therapy
- Asthma (bronchospasm can be caused by N-acetylcysteine)
- Phlebotomy in last 3 months
- h/o adverse reaction to acetazolamide or N-acetylcysteine
Trial locations and contacts
1 site in 1 country.
Peru1 site
Chronic mountain sickness clinic
Cerro de Pasco, Departamento de Pasco
About this study
Official title: Randomized Controlled Trial of N-acetylcysteine and Acetazolamide in Treatment of Chronic Mountain Sickness
Chronic mountain sickness is characterized by excessive red blood cell production which causes sludging of the vascular system. This high viscosity blood causes heart failure, cognitive dysfunction, and strokes. The investigators hypothesize that cobalt which has been previously been shown to be an environmental pollutant worsens the overproduction of red blood cells. The investigators plan to conduct a 6 week trial in which acetazolamide (already shown to improve chronic mountain sickness) and N-acetylcysteine (a drug that removes cobalt from the blood) are evaluated in their potential to improve chronic mountain sickness.
- Conditions
- Erythrocytosis, Mountain Sickness
- Being tested
- N-acetylcysteine, Acetazolamide, Placebo pills
- Keywords
- Cobalt, Excessive Erythrocytosis, Monge's Disease, Acetazolamide, N-acetylcysteine, Altitude Sickness, Chronic Mountain Sickness
- Medical subject headings
- Polycythemia, Altitude Sickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
Also called Given in gel capsules
NAC 600 mg oral once daily
AcetazolamideDrug
Also called Given in gel capsules
Acetazolamide 250 mg oral once daily
Placebo pillsDrug
1 (or 2 in the placebo group) empty gel capsules
| Study group | Role | What they receive |
|---|---|---|
| Placebo pills | Placebo comparator | Not described Receives: Drug: Placebo pills |
| Acetazolamide alone | Active comparator | Not described Receives: Drug: Acetazolamide; Drug: Placebo pills |
| N-acetylcysteine alone | Active comparator | Not described Receives: Drug: N-acetylcysteine; Drug: Placebo pills |
| Combination of N-acetylcysteine and acetazolamide | Active comparator | Not described Receives: Drug: N-acetylcysteine; Drug: Acetazolamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in Hematocrit, or fraction of plasma occupied by cellular elements at week 8
Spun hematocrit measured on portable machine
Measured: Baseline and week 8
Secondary outcomes (6)
Change from baseline in arterial blood gas values at week 8
Analyzed using portable machine. The values analyzed include serum pH, partial pressure of carbon dioxide, partial pressure of oxygen, and serum bicarbonate.
Measured: Baseline and week 8
Change from baseline Erythropoietin at week 8
Serum hormone that stimulates red blood cell production
Measured: Baseline and week 8
Change from baseline in serum and urine Cobalt at day 3
Will calculate spot clearance of cobalt
Measured: Baseline and day 3
Change in baseline urine protein at 8 weeks
Ratio of urine total protein to urine creatinine
Measured: Baseline and week 8
Change in baseline Chronic mountain sickness score at 8 weeks
Chronic Mountain Sickness Score Absent Mild Moderate Severe Headache 0 +1 +2 +3 Dizziness 0 +1 +2 +3 Failing Memory 0 +1 +2 +3 Fatigue 0 +1 +2 +3 Breathlessness 0 +1 +2 +3 Sleep disturbances 0 +1 +2 +3 Tinnitus 0 +1 +2 +3 Anorexia 0 +1 +2 +3 Cyanosis of lips, face, or fingers 0 +1 +2 +3 Hyperemia or prominent capillaries conjunctivae or laryngopharynx 0 +1 +2 +3
Measured: Baseline and week 8
Changes in baseline Serum electrolytes at day 3, 14 and week 8
Electrolytes, specifically monitoring serum potassium to treat serious hypokalemia (serum potassium < 3.0 meQ/L).
Measured: Baseline and Days 3, 14, and week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2010 (estimated)
- Study startJun 2013
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for ErythrocytosisStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 85 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Universidad Peruana Cayetano Heredia, Jackson, Brian, M.S., Thomas H Maren Foundation
- Responsible party
- Sponsor
- Investigators
- Richard Johnson, MD, Principal investigator, University of Colorado Denver Health Sciences CenterAbdias Hurtado, MD, Principal investigator, Universidad Peruana Cayetano HerediaRichard Fuquay, MD, Study director, University of Colorado Denver Health Sciences Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01187108
- Sponsor's protocol ID
- 10-0078
- Acronym
- CoCMS
- Status last verified
- May 2015
- First submitted
- 18 Aug 2010
- Last updated
- 15 May 2015
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jefferson JA, Escudero E, Hurtado ME, Pando J, Tapia R, Swenson ER, Prchal J, Schreiner GF, Schoene RB, Hurtado A, Johnson RJ. Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels. Lancet. 2002 Feb 2;359(9304):407-8. doi: 10.1016/s0140-6736(02)07594-3.
PubMed 11844517Jefferson JA, Escudero E, Hurtado ME, Kelly JP, Swenson ER, Wener MH, Burnier M, Maillard M, Schreiner GF, Schoene RB, Hurtado A, Johnson RJ. Hyperuricemia, hypertension, and proteinuria associated with high-altitude polycythemia. Am J Kidney Dis. 2002 Jun;39(6):1135-42. doi: 10.1053/ajkd.2002.33380.
PubMed 12046023Richalet JP, Rivera-Ch M, Maignan M, Privat C, Pham I, Macarlupu JL, Petitjean O, Leon-Velarde F. Acetazolamide for Monge's disease: efficiency and tolerance of 6-month treatment. Am J Respir Crit Care Med. 2008 Jun 15;177(12):1370-6. doi: 10.1164/rccm.200802-196OC. Epub 2008 Apr 3.
PubMed 18388356
Study at a glance
From the registry record, last updated by the sponsor on 15 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial of N-acetylcysteine and Acetazolamide in Treatment of Chronic Mountain Sickness
- ClinicalTrials.gov ID
- NCT01187108
- Acronym / sponsor ID
- CoCMS / 10-0078
- Conditions
- Erythrocytosis, Mountain Sickness
- Keywords
- Cobalt, Excessive Erythrocytosis, Monge's Disease, Acetazolamide, N-acetylcysteine, Altitude Sickness, Chronic Mountain Sickness
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 85 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Collaborators
- Universidad Peruana Cayetano Heredia, Jackson, Brian, M.S., Thomas H Maren Foundation
- Study start
- Jun 2013
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 23 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Chronic mountain sickness is characterized by excessive red blood cell production which causes sludging of the vascular system. This high viscosity blood causes heart failure, cognitive dysfunction, and strokes. The investigators hypothesize that cobalt which has been previously been shown to be an environmental pollutant worsens the overproduction of red blood cells. The investigators plan to conduct a 6 week trial in which acetazolamide (already shown to improve chronic mountain sickness) and N-acetylcysteine (a drug that removes cobalt from the blood) are evaluated in their potential to improve chronic mountain sickness.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo pills | Placebo comparator | Drug: Placebo pills |
| Acetazolamide alone | Active comparator | Drug: Acetazolamide, Drug: Placebo pills |
| N-acetylcysteine alone | Active comparator | Drug: N-acetylcysteine, Drug: Placebo pills |
| Combination of N-acetylcysteine and acetazolamide | Active comparator | Drug: N-acetylcysteine, Drug: Acetazolamide |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males over 17 years of age
- Hematocrit > 70%
- Chronic Mountain Sickness score (CMS) > 6
- Able to give informed consent and follow instructions in written Spanish
Key exclusion criteria (5 listed)
- CMS > 15
- Underlying lung disease, smoking, or oxygen therapy
- Asthma (bronchospasm can be caused by N-acetylcysteine)
- Phlebotomy in last 3 months
- h/o adverse reaction to acetazolamide or N-acetylcysteine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| N-acetylcysteineAlso: Given in gel capsulesNAC 600 mg oral once daily | Drug | Combination of N-acetylcysteine and acetazolamide, N-acetylcysteine alone |
| AcetazolamideAlso: Given in gel capsulesAcetazolamide 250 mg oral once daily | Drug | Acetazolamide alone, Combination of N-acetylcysteine and acetazolamide |
| Placebo pills1 (or 2 in the placebo group) empty gel capsules | Drug | Acetazolamide alone, N-acetylcysteine alone, Placebo pills |
Primary outcome
Change from baseline in Hematocrit, or fraction of plasma occupied by cellular elements at week 8
Time frame: Baseline and week 8
Spun hematocrit measured on portable machine
6 secondary outcomes
Change from baseline in arterial blood gas values at week 8
Time frame: Baseline and week 8
Change from baseline Erythropoietin at week 8
Time frame: Baseline and week 8
Change from baseline in serum and urine Cobalt at day 3
Time frame: Baseline and day 3
Change in baseline urine protein at 8 weeks
Time frame: Baseline and week 8
Change in baseline Chronic mountain sickness score at 8 weeks
Time frame: Baseline and week 8
Changes in baseline Serum electrolytes at day 3, 14 and week 8
Time frame: Baseline and Days 3, 14, and week 8
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 May 2015.
- Background: PubMed 11844517Jefferson JA, Escudero E, Hurtado ME, Pando J, Tapia R, Swenson ER, Prchal J, Schreiner GF, Schoene RB, Hurtado A, Johnson RJ. Excessive erythrocytosis, chronic mountain sickness, and serum cobalt levels. Lancet. 2002 Feb 2;359(9304):407-8. doi: 10.1016/s0140-6736(02)07594-3.
- Background: PubMed 12046023Jefferson JA, Escudero E, Hurtado ME, Kelly JP, Swenson ER, Wener MH, Burnier M, Maillard M, Schreiner GF, Schoene RB, Hurtado A, Johnson RJ. Hyperuricemia, hypertension, and proteinuria associated with high-altitude polycythemia. Am J Kidney Dis. 2002 Jun;39(6):1135-42. doi: 10.1053/ajkd.2002.33380.
- Background: PubMed 18388356Richalet JP, Rivera-Ch M, Maignan M, Privat C, Pham I, Macarlupu JL, Petitjean O, Leon-Velarde F. Acetazolamide for Monge's disease: efficiency and tolerance of 6-month treatment. Am J Respir Crit Care Med. 2008 Jun 15;177(12):1370-6. doi: 10.1164/rccm.200802-196OC. Epub 2008 Apr 3.
Related trials for Erythrocytosis
RecruitingPhase 1
A Phase 1 Study of AB521 Monotherapy and Combination Therapies in Renal Cell Carcinoma and Other Solid Tumors
Clear Cell Renal Cell Carcinoma, Solid Tumors
Not yet recruitingPhase 2
Phase IIA Study of Belzutifan in EPAS1-, EGLN1-, or VHL-Mutant Erythrocytosis
Erythrocytosis, Pulmonary Hypertension
Not yet recruitingObservational study
EVAluation of Erythrocytosis PRospEctive Cohort STudy
Erythrocytosis, Polycythemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Richard Johnson, MD principal investigator
University of Colorado Denver Health Sciences Center
Abdias Hurtado, MD principal investigator
Universidad Peruana Cayetano Heredia
Richard Fuquay, MD study director
University of Colorado Denver Health Sciences Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing N-acetylcysteine and Acetazolamide in people with Erythrocytosis and Mountain Sickness, run by University of Colorado, Denver at 1 site in Peru.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Peru. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in Hematocrit, or fraction of plasma occupied by cellular elements at week 8 (time frame: Baseline and week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01187108, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 May 2015.